Networked system of mobile communication platforms for nonpharmacologic constriction of a pupil

ABSTRACT

A networked system of ophthalmic stimulators for temporarily constricting eye-pupils comprises a set of ophthalmic stimulators, each ophthalmic stimulator including a mobile irradiation control system, to generate an irradiation control signal; an irradiation source, coupled to the irradiation control system, to generate an irradiation; and an irradiation delivery system, coupled to the mobile irradiation control system, to receive the irradiation from the irradiation source, and to deliver a patterned irradiation to an iris of the eye; wherein the mobile irradiation control system controls at least one of the irradiation source and the irradiation delivery system with the irradiation control signal so that the patterned irradiation causes a temporary constriction of the pupil of the eye, without causing a permanent constriction of the pupil; and a central station, including a central image processor, wherein the mobile irradiation control systems and the central station are configured to communicate through a communication network.

CROSS-REFERENCE TO RELATED PATENT DOCUMENTS

This application is a continuation-in-part of U.S. Patent Application:“System for temporary nonpharmacologic constriction of the pupil”, byRonald M. Kurtz and Gergely T. Zimanyi, with application Ser. No.15/293,269, filed on Oct. 13, 2016; hereby incorporated by reference inits entirety.

FIELD OF INVENTION

This invention relates to a system for pupil constriction, moreprecisely, to a system of temporary, non-pharmacological construction ofa pupil of an eye.

BACKGROUND

A number of devices that make use of the increased depth of field of asmall aperture have been proposed for use in ophthalmology, anddeveloped to improve vision. These devices are particularly promising toimprove near vision for those who have presbyopia. Examples of suchdevices include small aperture corneal inlays, reduced-apertureintraocular lenses, as well as other aperture implants that are meant toimpact light propagation along the visual axis. While effective, thesesurgically implanted permanent inlays carry the risk inherent with anyimplantable device, such as inflammation, infection, or displacementthat may require secondary surgical procedures to remove the implant andmay necessitate performing other procedures.

Pharmacological methods have also been proposed using medications suchas pilocarpine and other agents to temporarily constrict the pupil.While these drugs can temporarily improve vision, they generally requirefrequent instillation of drops, and can be associated with undesirableside effects, such as headaches.

An alternative approach has been proposed by Hickenbotham in US patentapplication 2013/0226161, which utilizes a laser to cauterize certainportions of the iris to cause a permanent constriction of the pupil.While this approach offers some advantages over implants andmedications, the permanent constriction of the pupil, achieved by acontrolled damaging of the iris dilator muscle, does not allow for atrial of the effect, and once performed, leaves the patient with apermanent deficit in iris function. In addition, the exact shape of theconstricted pupil may be difficult to control, and may result in odd,irregular, oval, or other undesired pupil shapes. Therefore, the medicalneed persists to develop a non-pharmacological, non-permanent visionimprovement that does not involve inserting a small-aperture objectsurgically into the eye.

In some embodiments, an ophthalmic stimulator for temporarilyconstricting a pupil of an eye comprises an irradiation control system,to generate an irradiation control signal; an irradiation source,coupled to the irradiation control system, to generate an irradiation;and an irradiation delivery system, coupled to the irradiation controlsystem, to receive the irradiation from the irradiation source, and todeliver a patterned irradiation to an iris of the eye; wherein theirradiation control system controls at least one of the irradiationsource and the irradiation delivery system with the irradiation controlsignal so that the patterned irradiation causes a temporary constrictionof the pupil of the eye, without causing a permanent constriction of thepupil.

In some embodiments, a method for temporarily constricting a pupil of aneye by an ophthalmic stimulator comprises generating an irradiationcontrol signal by an irradiation control system; generating anirradiation by an irradiation source, coupled to the irradiation controlsystem; receiving the irradiation and delivering a patterned irradiationto an iris of the eye with an irradiation delivery system; andcontrolling at least one of the irradiation source and the irradiationdeliver system by the irradiation control signal of the irradiationcontrol system so that the patterned irradiation is causing a temporaryconstriction of the pupil of the eye, without causing a permanentconstriction of the pupil.

In some embodiments, an ophthalmic stimulator for constricting a pupilof an eye comprises an irradiation control system, to generate anirradiation control signal; an irradiation source, coupled to theirradiation control system, to generate an irradiation; and anirradiation delivery system, coupled to the irradiation control system,to receive the irradiation from the irradiation source, and to deliver apatterned irradiation to an iris of the eye; wherein the irradiationcontrol system controls at least one of the irradiation source and theirradiation delivery system with the irradiation control signal so thatthe patterned irradiation causes a long-term constriction of the pupilof the eye.

In some embodiments, an ophthalmic stimulator for temporarilyconstricting a pupil of an eye comprises an irradiation control system,to generate an irradiation control signal; a light source, coupled tothe irradiation control system, to generate a light beam; and abeam-shaping optics, coupled to the irradiation control system, toreceive the light beam from the light source, and to deliver a lightring to an iris of the eye; wherein the irradiation control systemcontrols at least one of the light source and the beam-shaping opticswith the irradiation control signal so that the light ring causes atemporary constriction of the pupil of the eye, without causing apermanent constriction of the pupil.

In some embodiments, an ophthalmic stimulator for temporarilyconstricting a pupil of an eye comprises a digital beam controller, togenerate a digital beam-control signal; a light source, coupled to thebeam controller, to generate a light beam; and a digitally controlledbeam modulator, to receive the digital beam-control signal from the beamcontroller, to receive the light beam from the light source, and tomodulate the received light beam into a patterned light, delivered to aniris of the eye; wherein the beam controller controls at least one ofthe light source and the digitally controlled beam modulator with thedigital beam-control signal so that the patterned light causes atemporary constriction of the pupil of the eye, without causing apermanent constriction of the pupil.

In some embodiments, an ophthalmic stimulator for temporarilyconstricting a pupil of an eye comprises an irradiation control system,having a feedback system, to generate an irradiation control signalusing a feedback of the feedback system; an irradiation source, coupledto the irradiation control system, to generate an irradiation; and anirradiation delivery system, having a targeting system and coupled tothe irradiation control system, to receive the irradiation from theirradiation source, and to direct a patterned irradiation in a patternto a treatment region of an iris of the eye using the targeting system;wherein the irradiation control system controls at least one of theirradiation source and the irradiation delivery system with theirradiation control signal so that the patterned irradiation causes atemporary constriction of the pupil, without causing a permanentconstriction of the pupil.

In some embodiments, an ophthalmic stimulator for temporarilyconstricting a pupil of an eye comprises a mobile irradiation controlsystem, to generate an irradiation control signal; an irradiationsource, coupled to the irradiation control system, to generate anirradiation; and an irradiation delivery system, coupled to the mobileirradiation control system, to receive the irradiation from theirradiation source, and to deliver a patterned irradiation to an iris ofthe eye; wherein the mobile irradiation control system controls at leastone of the irradiation source and the irradiation delivery system withthe irradiation control signal so that the patterned irradiation causesa temporary constriction of the pupil of the eye, without causing apermanent constriction of the pupil.

In some embodiments, a networked system of ophthalmic stimulators fortemporarily constricting eye-pupils comprises a set of ophthalmicstimulators, each ophthalmic stimulator including a mobile irradiationcontrol system, to generate an irradiation control signal; anirradiation source, coupled to the irradiation control system, togenerate an irradiation; and an irradiation delivery system, coupled tothe mobile irradiation control system, to receive the irradiation fromthe irradiation source, and to deliver a patterned irradiation to aniris of the eye; wherein the mobile irradiation control system controlsat least one of the irradiation source and the irradiation deliverysystem with the irradiation control signal so that the patternedirradiation causes a temporary constriction of the pupil of the eye,without causing a permanent constriction of the pupil; and a centralstation, including a central image processor, wherein the mobileirradiation control systems of the of the ophthalmic stimulators and thecentral station are configured to communicate through a communicationnetwork.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 illustrates an eye 1.

FIGS. 2A-B illustrate the pupil under different illuminations.

FIGS. 3A-B illustrate an effect of applying an irradiation to the iris.

FIGS. 4A-B illustrate the effect of irradiation on the muscle response.

FIGS. 5A-B illustrate embodiments of the ophthalmic stimulator 100, andthe permanent ophthalmic stimulator 100′.

FIGS. 6A-D illustrate embodiments of the ophthalmic stimulator 100.

FIGS. 7A-F illustrate embodiments of the ophthalmic stimulator 100 witha beam shaping optics 134.

FIGS. 8A-B illustrate embodiments of the ophthalmic stimulator 100 witha digital beam controller 110.

FIGS. 9A-E illustrate embodiments of the beam modulator 134.

FIG. 10 illustrates an irradiation controller 112.

FIGS. 11A-D illustrate steps of the methods 300, 300′, 302, and 304.

FIGS. 12A-E illustrate embodiments of the alignment system 135.

FIGS. 13A-C illustrate mobile embodiment of the ophthalmic stimulator100.

FIG. 14 illustrates a mobile network of self-treatment stimulators 400.

FIG. 15 illustrates an embodiment of the feedback system, 116.

FIGS. 16A-E illustrate methods 510-550.

FIGS. 17A-D illustrate various irradiation patterns 210.

DETAILED DESCRIPTION

Embodiments of the invention address the above described needs in thefollowing manner. Some embodiments provide systems and methods for atemporary constriction of the pupil without the need of medicationtherapy. The duration of the constriction can be controlled by aselection of treatment parameters. In a suitable range of treatmentparameters, the procedure can be fully reversible: after acharacteristic time, the pupils return to essentially their originaldiameter without further treatment. The pupils can be re-constricted byapplying the treatment repeatedly. Therefore, the here-described methodsand devices provide the advantages of a temporary, but long lastingvision improvement, while avoid the hazards associated with (1) apertureimplants and inlays, inserted by a surgical procedure, (2) permanentdestruction of tissue, and (3) pharmaceutical approaches and theirundesirable side-effects.

Some embodiments achieve these advantages by heating the iris by anirradiation to a suitable temperature range, (1) to cause a temporaryinactivation of the iris dilator muscle, and, in some cases, (2) toenhance an action of the iris constrictor sphincter muscle. Thisirradiative heat treatment can be applied for a time sufficiently longto cause a reduction in contractile activity, but short enough to avoidcausing permanent tissue damage. While the detailed mode of action isyet to be clarified, this effect may be mediated by inactivation of theactin-myosin complex in the exposed muscle.

FIG. 1 shows a cross section of an eye 1. The eye 1 includes the wellknown constituents: a cornea 5, where light enters the eye 1, and asclera 7, an opaque, fibrous protective outer layer of the eye 1 thatcontains collagen and elastic fibers. Distal to the cornea 5 is ananterior chamber 9 that contains an aqueous humor. The anterior chamber9 is separated from a posterior chamber 15 by an iris 11. An opening ata center of the iris 11 is a pupil 13 that allows the light to proceedtoward the posterior segment of the eye 1. Behind the pupil 13, ciliarymuscles 17 hold a lens 19 in a central position. These ciliary muscles17 can also delimit the lens 19 as part of accommodating the vision tothe distance of the target the eye is looking at. With advancing age,the ciliary muscles 17 slowly loose their ability to deform and adaptthe lens 19 to varying vision distances: a condition typically referredto as presbyopia. Behind the lens 19 is a vitreous 21. As the lightcrosses the vitreous 21, it eventually hits the retina 23. The electricstimuli, generated by the incoming light in the retina 23, aretransmitted by the optic nerve 25 towards the brain.

FIG. 2A-B illustrate that the iris 11 includes a circular sphinctermuscle 40 around the pupil 13, capable of shrinking the perimeter of thepupil 13, thus constricting it. At the same time, the iris 11 alsoincludes radial dilator muscles 30 that specialize in expanding, orenlarging, the pupil 13. The competition of the sphincter muscles 40 anddilator muscles 30 determines the eventual radius of the pupil 13. FIG.2A illustrates in its left panel that in strong light the contractingsphincter muscles 40 constrict the pupil 13. FIG. 2A illustrates in itsmiddle panel the pupil 13 in an average light. FIG. 2A illustrates inits right panel that in low light conditions, the radial dilator muscles30 dominate the sphincter muscles 40 and dilate the pupil to enhance theamount of light directed to the retina 23.

FIG. 2B illustrates a cross section of the iris 11 from the side. It iswell visible that the sphincter pupillae 40 is positioned along the edgeof the pupil 13, the pupillary ruff while the radial dilator pupillae 30are located radially outward, farther from the edge of the pupil 13.

The anatomy of the muscles of the iris 11 is also important. The dilatormuscle 30 fibers are typically located near the distal portion of theiris 11, adjacent to the iris pigmented epithelium. In contrast, theconstrictor sphincter muscles 40 are more superficial and central,located towards the pupil's edge or margin. Details of the anatomy ofthese muscles can be found in much greater detail in Junqueira L. C.,Carneiro J. 2005. Basic Histology, Eleventh Edition. The McGraw-HillCompanies, Inc. United States of America.

FIGS. 3A-B illustrate a principle of embodiments of the invention. FIG.3A illustrates that a patterned irradiation can be applied to the iris11 for a limited time period, such as 1-100 seconds, with less timerequired when higher temperatures are applied. The pattern is typicallya ring of light, or light-ring. The irradiation raises the temperatureof the iris 11 in a treatment region. The tissue of the iris 11 can beheated to temperatures that are not sufficient to cauterize or destroythe tissue, but are capable of reducing an activity, or responsivenessof the targeted tissues.

FIG. 3B illustrates the outcome of the irradiation. The heat treatmentreduces the activity of the iris dilator muscle and this allows thepupillary constrictor, or sphincter, muscle to reduce the pupil'sdiameter. Reducing the pupil's diameter reduces the aberrations of theimaging of the eye, sometimes referred to as the pinhole effect inoptics. Reducing the aberrations extends the depth of focus, and therebycompensates the emergence of presbyopia in an aging eye. Since thismethod utilizes the natural constrictor muscle to effect the pupil sizechange, the risk of pupil de-centration is less than in the case ofsurgical implants, discussed previously.

FIGS. 4A-B illustrate that heat treatments have been already studied anddemonstrated to reduce muscle activity in human tissues, such as in thelung and the prostate, which have smooth muscle tissues similar to thatof the iris. The heat treatment can reduce, or inhibit, muscle activityin these tissues. The duration of inactivity can last for hours to daysin these systems (see Am. J. Respir. Cell Mol. Biol. Vol 44. pp 213-221,2011). FIG. 4A illustrates the effect of heat treatments on lung smoothmuscle. The muscle tissue was heated for a treatment time between 5 sand 60 s. After the heat treatment, a test stimulus was administered tothe heat-treated and the untreated muscles. The graph reports the ratioof responses to this test as a function of the treatment temperature ofthe tissue. Visibly, as the treatment temperature exceeded 50 Celsius,or Centigrade, the response of the treated muscle to the test stimulusgradually decreased. For heat treatments above 55-60 Celsius, theresponse became negligible: the muscle was deactivated by the treatment.

FIG. 4B illustrates the same ratio of responses of treated muscles tonon-treated muscles, with the difference that it indicates how long theeffect lasted. As the curves show, the de-activation of the smoothmuscle with heat treatments raising the muscle temperature above 50-55Celsius lasted at least for 28 hours, and possibly longer. Thisremarkably long-lasting deactivation of smooth muscle in response tosuch a mild and short temperature increase is utilized by embodimentsdescribed in this document.

FIG. 5A illustrates an ophthalmic stimulator 100 for temporarilyconstricting a pupil 13 of an eye 1, building on the just-describedobservations, comprising an irradiation control system 110, to generatean irradiation control signal; art irradiation source 120, coupled tothe irradiation control system 110, to generate an irradiation 200; andan irradiation delivery system 130, coupled to the irradiation controlsystem 110, to receive the irradiation 200 from the irradiation source120, and to deliver a patterned irradiation 200 p to an iris 11 of theeye 1 in a pattern 210. In embodiments, the irradiation control system110 controls at least one of the irradiation source 120 and theirradiation delivery system 130 with the irradiation control signal sothat the patterned irradiation 200 p causes a temporary constriction ofthe pupil 13 of the eye 1, without causing a permanent constriction ofthe pupil 13.

The irradiation control system 110 can include a memory, to storeexecutable programs and applications; a processor, to execute at leastone of a stored program and an installed application; and a userinterface, to receive input from a user in relation to an operation ofthe memory and the processor.

In some embodiments of the ophthalmic stimulator 100, the irradiationsource 120 can include an incoherent light source, such as a lightsource, a LED, a lamp, an infrared source, a broad-band source, anarrow-band source, a radio-frequency source, an electromagneticradiation source, or a sound source, to generate a light beam, anelectromagnetic irradiation, an infrared beam, a LED light, or a sound.A separate class of irradiation sources can include a coherent lightsource, such as a laser, a pulsed laser, or a continuous wave (CW)laser.

The just discussed classes of incoherent and coherent irradiationsources have different advantages and drawbacks. Lasers offer goodcontrol and unparalleled precision. At the same time, laser beams have avery small diameter, often less than 100 microns. Therefore, to affectlarger treatment regions, they require a complex and expensive,digitally controlled optical system, such as a scanning system. Theselaser-plus-scanning systems offer great control and precision. At thesame time, they can be expensive, and can introduce multiple sources ofunreliability and performance degradation, a potential problem inmedical applications, where high reliability is essential. Using lasersand scanners may therefore necessitate regular maintenance. Also, laserbeams can be very intense, thus if a laser gets pointed to an unintendedpart of an ophthalmic tissue, it can cause substantial damage.Therefore, much stronger safety systems and precautions are needed inlaser systems.

In contrast, non-coherent light sources, such as LEDs, infrared sources,lamps, infrared sources, and others may offer less precision andcontrol. However, this control may be sufficient for the purposes of thehere-described treatment. Also, incoherent light sources can make theophthalmic stimulator 100 much simpler, lighter, and smaller at the sametime. Since they typically do not require a digitally controlledscanning system, these incoherent light sources can also be cheaper tomaintain and can be more robust and reliable. Finally, since these lightsources are less intense, systems with incoherent light sources mayrequire less stringent safety systems and measures. All in all, acomparative analysis of the competing advantages and disadvantages isperformed when a system designer decides whether to use a coherent, oran incoherent light source as the irradiation source 120 of theophthalmic stimulator 100.

Embodiments of the ophthalmic stimulator 100 can be characterized bynumerous treatment parameters. These treatment parameters can includethe followings. A power density of the patterned irradiation 200 p ofthe irradiation delivery system 130 can be in the range of 0.1-1000mW/cm², in some designs in the range of 1-100 mW/cm². A total powerdelivered by the patterned irradiation 200 p to the iris can be in therange of: 0.1-1,000 mW, in some designs in the range of 1-100 mW. Atotal energy, deposited by the patterned irradiation 200 p during thetreatment can be in the range of 10 microJ-10 J, in some designs in therange of 100 microJ-100 mJ.

A wavelength of the irradiation source 120 can be in the range of400-4,000 nm, in some designs, in the range of 600-1,500 nm. Thewavelength of some stimulators 100 can be selected by noting in FIG. 2B,that the muscle fibers of the radial dilators 30 are located in theproximity of the pigmented epithelium of the iris 11. This fact can beused to selectively target and heat the dilator muscles 30 indirectly.The pigmented epithelium layers may not have essential functions thatwould be negatively affected by heating, such as undergoing anirrecoverable reactivity change. To build on this, irradiation sources120 can emit the irradiation 200 with a wavelength close to thewavelength where the absorption of the pigmented epithelium shows amaximum, or is at least greatly enhanced. Such irradiation sources 120can heat the pigments particularly efficiently, possibly to temperatures55 C, 60 C, possibly even to 60-65 Celsius. The heated pigmentedepithelia can then provide a secondary, or indirect heating to thedilator muscles 30, located in their immediate proximity, to themedically preferred 50-55 Celsius temperatures.

FIG. 2B also illustrates that the dilator muscles 30 are in the distalregion of the iris 11. Therefore, irradiation with wavelengths thatpenetrate the iris tissue more efficiently and to greater depths can befavored to make sure that the dilator muscles 30 are well heated. Inseveral ophthalmologic studies, irradiation with longer wavelengthsshowed greater penetration into ophthalmic tissues. Therefore, someirradiation sources 120 may emit irradiation 200 with longer wavelengthsto penetrate more deeply into the iris, with eventual absorption by thepigmented epithelium, to achieve secondary heating of the dilator musclefibers 30. Accordingly, a depth of a treated tissue within the iris canbe in some designs in the range of 10 microns-3,000 microns, in somedesigns, in the range of 500-2,000 microns.

Some irradiation sources may emit a continuous, or continuous wave (CW)irradiation 200. Others, such as lasers, or LEDs, may emit pulsedirradiation. A frequency of the pulsed irradiation 200 can be in a rangeof 1 Hz to 1 MHz, in some designs, in the range of 100 Hz to 100 kHz.The length of the emitted pulses can vary from 10 femtoseconds to 1second, in some designs from 1 microsecond to 1 millisecond. The totaltreatment time can be in the range of 1 sec to 300 sec, in someembodiments in the range of 10 sec to 100 sec. A beam profile of thepatterned irradiation 200 p can be a rectangular, a flat top, asmoothed, a Gaussian, or a Lorentzian profile.

An inner radius Rp(inner) of the pattern 210 can be in the range of 2-10mm, in some designs in the range of 3-6 mm. An outer radius Rp(outer) ofthe pattern 210 can be in the range of 3-15 mm, in some designs, in therange of 5-10 mm The pattern 210 can be such that a treated fraction ofthe iris has an area that is 10-80% of the total area of the iris 11, insome design, this fraction can in the range of 20-50%.

In some embodiments, the irradiation delivery system 130 can include apattern generator, an optical beam shaper, a patterning optics, a beamprofiler, or a digitally controlled irradiation optics. Some of theseelements can be built mostly from passive optical elements, such aslenses and mirrors, with some system characteristics controlledelectronically, such as a telescopic distance between two lenses. Inother embodiments, the irradiation delivery system 130 can includeoptical elements that are actively operated and controlled by electronicor digital circuitry, as described below.

Some embodiments of the ophthalmic stimulator 100 can be configured toincrease a temperature of a treatment region of the iris to a range of45-60 degrees Celsius. Other embodiments can increase the temperature ofthe treatment region of the iris to a range of 50-55 degrees Celsius. Asdiscussed in relation to FIGS. 4A-B, treatments with temperatures inthese ranges have been demonstrated to impact the responsiveness ofsmooth muscle tissue temporarily, in a reversible and repeatable manner.

The actual effect of the heat treatment depends on several factors,since different temperatures and treatment durations can have amultitude of effects on smooth muscle cells and function. On thecellular level, first, a heat treatment can induce biochemical changesand secretions that can affect the functioning of the treated tissue,such as heat shock proteins. Second, it can cause loss of cells throughvarious mechanisms, such as apoptosis, or programmed cell death.Finally, on a much shorter time scale, heat treatment can lead tospecific loss of contractility due to denaturation of myosin moleculesor inhibition of ion channels.

On a higher, physiological level, the effect of the heat treatment onthe pupil may depend on factors such as dilator muscle fiberorientation, and on opposing, constrictor, muscle action. Finally, theheat treatment can change the physical properties of the muscles indifferent aspects as well, including shrinking or expanding the lengthof the muscle strands, making the strands more or less aligned, andchanging of the elastic moduli of the muscles, among others.

For all these reasons, the iris of the individual patients can beanalyzed by the ophthalmologist before the treatment with the ophthalmicstimulator 100. Based on the analysis, the desired medical outcomes canbe cross-referenced with the patient data of the individual patients.Subsequently, the treatment region, treatment parameters andspecifically the treatment temperatures can be set. As discussed furtherbelow, for some medical outcomes heating the radial dilator muscles 30can be preferable, for others, heating the circular sphincter muscles 40can be preferable. The treatment regions can be set according to thesemedical considerations.

FIGS. 6A-D illustrate that in some embodiments of the ophthalmicstimulator 100, the irradiation control system 110 can include anirradiation controller 112, an imaging system 114 and a user interface118. The imaging system 114 can be electronically coupled to theirradiation controller 112, to relay images, image-related data, andcontrol information. The imaging system 114 can include an imageprocessor 114 ip, whose functions will be described later.

FIGS. 6A-B illustrate two implementations of the imaging system 114. InFIG. 6A, an imaging light 220 is reflected out from the optical pathwayof the patterned irradiation 200 p by a beam splitter 131 towards theimaging system 114 that is positioned outside the irradiation opticalpathway. In FIG. 6B, a small imaging system, such as a small CCD camera114 can be placed on the distal end of the irradiation delivery system130, directly receiving the imaging light 220. The imaging light 220 canbe a reflection of an imaging light, projected on the iris 11 by animaging light source. In other designs, the imaging light 220 can besimply the ambient light reflected from the iris 11.

The imaging system 114 can be any one of the well known ophthalmicimaging systems, including a CCD camera, feeding into a video monitor,any other electronic or digital imaging system, a video microscope, or asurgical microscope.

The irradiation control system 110 can generate the irradiation controlsignal by generating an image of the iris 11 of the eye with the imagingsystem 114 for a user, followed by receiving an image-based input fromthe user through the user interface 118, and generating the irradiationcontrol signal to control the irradiation delivery system 130 to deliverthe patterned irradiation 200 p in accordance with the receivedimage-based input.

In a typical example, the patterned irradiation 200 p can impact theiris 11 in a ring pattern 210 with an inner radius Rp(inner) and anouter radius Rp(outer). In this embodiment, the user of the system, suchas ophthalmologist, or an ophthalmic surgeon, can be prompted via theuser interface 118 to enter the image-based input, which in this casecan be a selection of the inner radius Rp(inner) and the outer radiusRp(outer) of the ring pattern 210, based on the surgeon analyzing theimage, relayed by the imaging system 114.

FIGS. 12D-E illustrate that setting these radii Rp(inner) and Rp(outer)determines whether the ring pattern 210, and thus the treatment region,is the region of the radial dilator muscles 30, or the circularsphincter muscles 40. Denoting the outer radius of the sphincter muscleswith R(sphincter), if the surgeon selects the inner radius Rp(inner) ofthe ring pattern 210 to be greater than R(sphincter):Rp(inner)>R(sphincter), then the ring pattern 210 will fall on theradial dilator muscles 30, and those muscles will receive the heattreatment. Whereas, if the surgeon selects the outer radius Rp(outer) ofthe ring pattern 210 to be smaller than R(sphincter):Rp(outer)<R(sphincter), then the ring pattern 210 will fill on thecircular sphincter muscles 40, and the circular sphincter muscles 40will be treated by the patterned irradiation 200 p. As discussed, anophthalmologist can select either treatment region based on a prioranalysis of the patient's specific data, and the desired medicaloutcomes.

In some embodiments, the irradiation control system 110 can include animage processor 114 ip in the imaging system 114. The image processor114 ip can be integrated with the imaging system 114, can be partiallyintegrated, or can be a separate electronic or computational system. Inthese embodiments, the irradiation control system 110 can generate theirradiation control signal by generating an image of the iris 11 withthe imaging system 114 for the image processor 114 ip, receiving animage-based input from the image processor 114 ip, and generating theirradiation control signal to control the irradiation delivery system130 to deliver the patterned irradiation 200 p in accordance with thereceived image-based input.

In a representative embodiment, the patterned irradiation 200 p canimpact the iris 11 in a ring pattern 210 with inner and outer radiiRp(inner) and Rp(outer). The imaging system 114 can image the iris 11,and relay this image to the image processor 114 ip, in response, theimage processor 114 ip can run an image recognition program, possiblyincluding an edge-recognition software, and identify the inner and outerradii of the iris 11, and the radius R(sphincter) that demarcates theradial dilator muscles 30 from the circular sphincter muscles 40. Then,the image processor 114 ip can generate the image-based input that sets,or suggests to set, the Rp(inner) and Rp(outer) radii of the ringpattern 210. The effect of these choices on the treatment region and thecorresponding medical effects have been explained earlier.

FIG. 12A-C illustrate that in some embodiments of the ophthalmicstimulator 100, the irradiation control system 110 can include analignment system 135.

FIG. 12A illustrates that in some embodiments the ophthalmic stimulator100 can include an objective 133, the last optical element that guidesthe patterned irradiation 200 p toward the eye 1. In these embodiments,the alignment system 135 can include a frame, or chin-rest 136, on whichthe patient can rest her/his chin to minimize the motion of the eye 1relative to the stimulator 100. The alignment system 135 can alsoinclude a patient interface 137 that contacts the eye 1 of the patient.Many types of patient interfaces 137 are known in the art and can beused here. FIG. 12A illustrates a patient interface 137, whose proximalend is attached to the objective 133 of the ophthalmic stimulator 100,and whose distal end the patient presses her eyes against. The patientinterface 137 can ensure a firm coupling, or docking, to the eye byinvolving a vacuum suction system, or a forceps. The patient interface137 can be a one-piece or a two-piece patient interface. The distal endof the patient interface 137 can include a contact lens, to ensure asmoother, softer connection to the eye. Such a contact lens alsominimizes the optical distortions of the patterned irradiation 200 p asit exits the patient interface 137 and enters the cornea 5 of the eye 1.

FIG. 12B illustrates another embodiment of the alignment system 135,where the patient interface 137 is coupled to the frame 136 instead ofthe stimulator 100. Since the frame 136 is rigidly coupled to theophthalmic stimulator 100, the optical pathway of the patterned light200 p is similarly secure from the objective to the eye 1 in thisembodiment as well. One of the differences is that there is a distancebetween the stimulator 100 and the patient interface, 137, so thepatient does not have to lean forward to receive the treatment, and thedoctor sees where the patterned light 200 p hits the patient interface137. As before, this patient interface 137 can also be a one-piece and atwo-piece patient interface 137.

The patient interfaces 137 of either FIG. 12A or 12B is preferablyaligned and centered with the eye 1 before coupling, or docking them tothe eye 1. FIG. 12C illustrates a corresponding aligning, or centering,pattern 138 of the alignment system 135. This centering pattern, oraligning pattern, can include an aligning ring 138 a, or an aligningcross-hair 138 b, or both. This aligning pattern 138 can be formed in,projected into, or digitally overlaid, the image formed by the imagingsystem 114, in a position that is concentric with the optical axis ofthe objective 133. The ophthalmic surgeon, or any other user oroperator, can dock the patient interface 137 of the stimulator 100 tothe eye with increased precision, with aligning, or centering, thealigning element 138 with the pupil 13 during the docking procedure.

In a video-monitor-based embodiment, the surgeon can make the centeringof the aligning ring 138 a on the video image with the edge of the pupil13 part of the docking. During the docking, the surgeon can instruct thepatient to move her/his head and eye around, until the circular edge ofthe pupil 13 is concentric with the aligning ring 138 a. Then thesurgeon can complete the docking of the patient interface 137 to the eye1. Further embodiments of the alignment system 135 will be describedlater.

In some designs, the stimulator 100 can include a fixation light 202,and the surgeon can instruct the patient to stare at the fixation light202 during docking. The patient staring, or fixating at the fixationlight 202 can further help centering the patient interface 137 with thepupil 13 during the docking.

In these embodiments, the irradiation control system 110 can generatethe irradiation control signal by processing alignment data with thealignment system 135, and generating the irradiation control signal tocontrol the irradiation delivery system 130 to deliver the patternedirradiation 200 p to the iris in a pattern 210 aligned with the pupil 13of the eye.

In some embodiments of the ophthalmic stimulator 100, the processingalignment data can include generating an image of the iris 11 with theimaging system 114, and overlaying an alignment pattern 138 on thegenerated image. The generating the irradiation control signal caninclude generating a misalignment-warning signal, or generating analignment-guidance signal, if a misalignment is detected during theprocessing of the alignment data that is part of the docking. Themisalignment-warning signal can alert the operating surgeon to instructthe patient to move his/her head, eye, or both to improve the alignmentto help making the docking precise. Also, for stimulator designs wherethe stimulator 100 or the patient interface 137 itself can be moved oradjusted, the misalignment-warning signal can alert the surgeon for theneed to adjust the stimulator 100 or the patient interface 137.

An example for an adjustable patient interface 137 is a two-piecepatient interface 137, where one piece of the patient interface 137 canbe attached to the stimulator 100 at its objective 133, the other pieceof the patient interface 137 can be coupled to the eye withvacuum-suction, or pressing, and the docking includes the surgeonmaneuvering the two pieces of the patient interface 137 to dock to eachother.

FIGS. 6C-D also show a feedback system 116. This system will bedescribed in detail below.

FIG. 10 illustrates that the irradiation controller 112 can include anumber of blocks. These blocks can be implemented as a dedicatedprocessor or circuitry, or can be implemented as a software, code,program, or application, implemented on a computer of the irradiationcontroller 112, or a combination of hardware and software blocks. Invarious embodiments, the irradiation controller 112 can include:

-   -   a feedback block 112 a, to receive feedback data and to send a        feedback signal to a processor 113;    -   an imaging block 112 b, to receive imaging data and to send an        imaging signal to the processor 113;    -   an alignment block 112 c, to receive alignment data and to send        an alignment signal to the processor 113;    -   a memory block 112 d, to receive patterns for storage and        patient data, to store algorithms and codes, and to send stored        patterns, patient data, or executable algorithms to the        processor 113;    -   a pattern generator block 112 e, to receive pattern parameters        and to send generated patterns to the processor 113;    -   a user interface block 112 f, to receive a user input, for        example through a user interface 118, that can be patterns,        commands, and irradiation parameters, and to send the received        patterns, commands and irradiation data as a user input signal        to the processor 113.

Each of these blocks can receive, their input from correspondinghardware blocks, such as sensors, controllers, hardware blocks and userinterfaces. For example, the feedback block 112 a can be a dedicatedcircuitry that receives the feedback data from the feedback system 116,as described below. The imaging block 112 b can be a software algorithm,implemented on a processor that receives the imaging data from theimaging system 114 that can include a CCD camera, a video monitor, or asurgical microscope.

In response to signals, received from any of the blocks 112 a-f, theprocessor 113 can send an irradiation control signal to the irradiationsource 120, or to the irradiation delivery system 130, or to both.

In some detail, in embodiments of the ophthalmic stimulator 100 theirradiation control system 110 can include the memory 112 d, and thegenerating the irradiation control signal can include recalling storeddata from the memory 112 d, representing at least one of an irradiationpattern and patient data, and generating the irradiation control signalto control the irradiation delivery system 130 to deliver the patternedirradiation 200 p to the iris 11 in accordance with the recalled storeddata.

In embodiments, the irradiation control system 110 can include a patterngenerator; and the generating the irradiation control signal can includegenerating an electronic representation of the irradiation pattern 210;and generating the irradiation control signal to control the irradiationdelivery system 130 to deliver the patterned irradiation 200 p with thegenerated irradiation pattern 210.

Returning to the medial effects and treatments, embodiments of theophthalmic stimulator 100 can cause a temporary constriction of thepupil 13 of the eye that includes an at least 5% reduction of a radiusof the pupil 13 that lasts less than one hour. In some cases, thereduction of the radius of the pupil can last for a time interval morethan one hour and less than one day. In other embodiments, the temporaryconstriction of the pupil of the eye includes an at least 5% reductionof the radius of the pupil that lasts for a time interval between oneday and one week; or between one week and one month; or between onemonth and three months; or between three months and one year.

Each of these time intervals has their own medical and patientadvantages. The longer the pupil constriction lasts, the less often thetreatment may need to be applied, which can be preferred by patients.Also, the overall paradigm of use of the ophthalmic stimulator 100depends on the duration of the constriction. Stimulators that constricta pupil for a month or longer can be deployed in the offices ofophthalmologists, and patients can schedule regular visits forre-constriction treatments on a monthly basis. Stimulators thatconstrict the pupil for a day or longer could be tabletop systems thatthe individual patients buy, or lease, and they self-administer thetreatment, for example, as part of a daily routine. Finally, stimulatorsthat constrict the pupil for an hour, or for a few hours, can be mobilesystems which the patient can carry with themselves and apply thetreatment on demand. Obviously, stimulators operated by untrainedpatients have to have much more robust safety, monitoring and controlsystems to prevent undesirable medical outcomes. In sum, embodimentsthat constrict the pupil for different time intervals can offer verydifferent medical outcomes, may be operated by very different personnel,and may need very different safety, monitoring and control systems.

FIG. 11A illustrates embodiments of a method 300, related for thepreceding description, for temporarily constricting a pupil 13 of an eyeby an ophthalmic stimulator 100. The method 300 includes the followingsteps:

-   -   generating 310 an irradiation control signal by an irradiation        control system 110;    -   generating 320 an irradiation 200 by an irradiation source 120,        coupled to the irradiation control system 110;    -   receiving 330 the irradiation 200, and delivering 332 a        patterned irradiation 200 p to an iris 11 of the eye with an        irradiation delivery system 130; and    -   controlling 340 at least one of the irradiation source 120 and        the irradiation delivery system 130 by the irradiation control        signal of the irradiation control system 110 so that the        patterned irradiation is causing a temporary constriction of the        pupil of the eye, without causing a permanent constriction of        the pupil.

In embodiments, the generating 320 the irradiation 200 can includegenerating a light beam, an electromagnetic irradiation, a LED light, anarrow-band light, a broad-band light, an infrared beam, an incoherentlight, a radio-frequency beam, or a sound by the irradiation source 120.Another class of irradiation sources 120 can include a coherent lightsource, a laser beam, a continuous wave laser beam, or a pulsed laserbeam. Marked differences between the preceding incoherent irradiationsources and the just-listed coherent and laser sources will be discussedbelow.

The delivering 332 of the patterned irradiation 200 p can includepatterning the irradiation 200 by at least one of a pattern generator112 e, an optical beam shaper 132, a patterning optics, a beam profiler,a beam scanner 134, and a digitally controlled irradiation optics.

In embodiments, the causing the temporary constriction of the pupil caninclude increasing a temperature of a treatment region of the iris to arange of 45-60 degrees Celsius. In some embodiments, the temperature ofthe treatment region of the iris can be raised into a range of 50-55degrees Celsius.

FIG. 10 illustrates, that in some embodiments of the method 300, theirradiation control system 110 can include an imaging system 114, insome cases with a corresponding imaging block 112 b in the irradiationcontroller 112, and a user interface 118, in some cases with acorresponding user interface block 112 f in the irradiation controller112. In these embodiments, the generating 310 of the irradiation controlsignal can include generating an image of the iris 11 of the eye withthe imaging system 114 for a user, receiving an image-based input fromthe user through the user interface 118, and generating the irradiationcontrol signal to control the irradiation delivery system 130 to deliverthe patterned irradiation 200 p in accordance with the received input.In embodiments, the patterned irradiation 200 p can impact the iris in aring pattern 210; and the image-based input can be an inner radiusRp(inner) and an outer radius Rp(outer) of the ring pattern 210,selected by the user.

In some embodiments of the method 300, the irradiation control system110 can include an imaging system 114, and an image processor 114 ip, insome cases implemented in the imaging block 112 b of the irradiationcontroller 112. The generating 310 of the irradiation control signal caninclude generating an image of the iris of the eye with the imagingsystem 114 for the image processor 114 ip; processing the image of theiris and generating an image-based input by the image processor 114 ip;receiving the image-based input from the image processor 114 ip; andgenerating 310 the irradiation control signal to control the irradiationdelivery system 130 to deliver the patterned irradiation 200 p inaccordance with the received image-based input. In some designs, thepatterned irradiation 200 p can impact the iris 11 in a ring pattern210; and the image-based input can be an inner radius Rp(inner) and anouter radius Rp(outer) of the ring pattern.

In some embodiments of the method 300, the irradiation control system110 can include an alignment system 135, in some cases with itsalignment block 112 c in the irradiation controller 112; and thegenerating 310 of the irradiation control signal can include processingalignment data with the alignment system 135, and generating theirradiation control signal to control the irradiation delivery system130 to deliver the patterned irradiation 200 p to the iris in a pattern210 aligned with the pupil 13 of the iris 11.

In some embodiments of the method 300, the processing alignment data caninclude generating an image of the iris with an imaging system 114, andoverlaying an alignment pattern 138 on the image, in some cases with thealignment block 112 c, or with the image processor 114 ip; and thegenerating 310 the irradiation control signal can include generating amisalignment warning signal, or generating an alignment-guidance signal.

In some embodiments, the irradiation control system 110 can include amemory block 112 d; and the generating the irradiation control signal310 can include recalling stored data from the memory block 112 d,representing at least one of an irradiation pattern 210 and patientdata; and generating 310 the irradiation control signal to control theirradiation delivery system 130 to deliver the patterned irradiation 200p to the iris 11 in accordance with the recalled stored data. In somedesigns, the irradiation control system can include the patterngenerator 112 e; and the generating 310 of the irradiation controlsignal can include generating the irradiation pattern 210; andgenerating the irradiation control signal to control the irradiationdelivery system 130 to deliver the patterned irradiation 200 p with thegenerated irradiation pattern 210.

Some embodiments of the method 300 can include acquiring and analyzingpatient data; selecting a treatment region based on the analyzing of thepatient data; and delivering the patterned irradiation 200 p to theselected treatment region. A notable embodiment of this step is theophthalmologist analyzing patient data and deciding whether thetreatment radiation shall be applied to the radial dilator muscles 30,or to the circular sphincter muscles 40. This analysis and decision caninvolve selecting the appropriate treatment parameters among the largenumber of treatment parameters described previously.

In some cases, the selecting the treatment region can include selectinga ring pattern 210 r with an inner radius Rp(inner) larger thanR(sphincter), a radius of a region of the circular sphincter muscles 40.

In some cases, the selecting the treatment region can include selectinga ring pattern 210 r with an outer radius Rp(outer) smaller thanR(sphincter), the radius of a region of the circular sphincter muscles40.

Some embodiments of the method 300 can include controlling theirradiation source 120, or the irradiation delivery system 130, or both,so that the patterned irradiation 200 p is causing a temporaryconstriction of the pupil of the eye that includes an at least 5%reduction of a radius of the pupil that lasts less than one hour.

In some cases, the temporary constriction of the pupil can last betweenone hour and one day. In some cases, the temporary constriction of thepupil can last between one day and one week; in some cases between oneweek and one month; in some cases between one month and three months;and in some cases between three months and one year. The medical,patient, implementation, and safety differences between embodimentsinvolving temporary constrictions of different duration have beendiscussed earlier.

The ophthalmic stimulators 100 described up to now shared a commontrait: they caused a temporary constriction of the pupil.

FIG. 5B illustrates a distinct class of permanent ophthalmic stimulators100′ that can cause a long-term, or even a permanent constriction of thepupil. These ophthalmic stimulators 100′ share some of the majorengineering elements with the temporary constriction stimulators 100,but have different medical modes of action, different irradiationsources, and stronger safety systems, among others.

In some embodiments, an ophthalmic stimulator 100′ for constricting apupil of an eye can include an irradiation control system 110′, togenerate an irradiation control signal; an irradiation source 120′,coupled to the irradiation control system 110′, to generate anirradiation 200′; and an irradiation delivery system 130′, coupled tothe irradiation control system 110′, to receive the irradiation 200′from the irradiation source 120′, and to deliver a patterned irradiation200 p′ to the iris 11 of the eye 1; wherein the irradiation controlsystem 110′ controls the irradiation source 120′, or the irradiationdelivery system 130′, or both, with the irradiation control signal sothat the patterned irradiation 200 p′ causes a long-term constriction ofthe pupil of the eye.

In a class of the ophthalmic stimulator 100′, the irradiation source120′ can include an incoherent light source, such as a lamp, a LED, aninfrared light source, a radiofrequency source, an electromagneticsource and a sound source. In another class, the irradiation source 120′can include a coherent light source, such as laser, a pulsed laser and acontinuous wave laser. There are substantial differences betweenirradiation sources that employ incoherent light sources and those thatemploy coherent light sources, as discussed above.

In some embodiments, the irradiation delivery system 130′ can include anoptical beam shaper and a patterning optics.

In some embodiments, the ophthalmic stimulator 100′ can be configured toincrease a temperature of a treatment region of the iris to a range of50-80 degrees Celsius. In some embodiments, the ophthalmic stimulator100′ can be configured to increase a temperature of the treatment regionof the iris to a range of 55-70 degrees Celsius.

Some embodiments of the ophthalmic stimulator 100′ can cause a long-termconstriction of the pupil that lasts longer than a year. In some cases,the ophthalmic stimulator 100′ can be designed to cause an irreversiblechange in the iris of the eye. This long-term, or permanent, change canbe a change of the length, or spatial extent, of the treated muscletissue. In other cases, it can be a reduced, or enhanced, elasticity, orflexibility. In some cases, it can be an altered stiffness. In somecases, it can be an altered reactivity to stimuli.

The ophthalmic stimulator 100′ achieves the long-term reduction ofconstriction of the pupil by applying the irradiation 200′ withtreatment parameters critically different from the ones used by thetemporary stimulator 100. The critical difference can be one of manyfactors that cause permanent, or long-term constriction of the pupil,including the followings. Beams with wavelength short enough to causepermanent change. Beams with intensity per area high enough to causelong-term change. Beams with total deposited energy high enough to causepermanent change. Beams with treatment times long enough to causepermanent change. Beams with beam pulses long enough, and frequencieshigh enough to cause permanent change. Which specific parameters aresufficient to make the change permanent is patient specific and isselected by the surgeon.

In some embodiments, the irradiation control system 110′ can include animaging system 114′ and a user interface 118′. In these embodiments, theirradiation control system 110′ can, generate the irradiation controlsignal by generating an image of the iris of the eye with the imagingsystem 114′ for a user, receiving an image-based input from the userthrough the user interface 118′, and generating the irradiation controlsignal to control the irradiation delivery system 130′ to deliver thepatterned irradiation 200 p′ in accordance with the received input.

Some of the engineering details of the permanent ophthalmic stimulator100′ are analogous to that of the temporary ophthalmic stimulator 100′.To contain the length of this document, some of these details of thestimulator 100′ will not be provided with their own figures, but thecorresponding figures in the description of the stimulator 100 will bereferenced, with the understanding that those need to be modified tocause a long term, not temporary constriction of the pupil.

In some embodiments of the ophthalmic stimulator 100′, the irradiationcontrol system 110′ can include an alignment system 135′; and theirradiation control system 110′ can generate the irradiation controlsignal by processing alignment data with the alignment system 135′, andgenerating the irradiation control signal to control the irradiationdelivery system 130′ to deliver the patterned irradiation 200 p′ to theiris in a pattern 210, aligned with a pupil 13 of the iris 11.

FIG. 11B illustrates a related method 300′ for causing a long-termconstriction of a pupil of an eye by the ophthalmic stimulator 100′. Themethod 300′ can include the following steps:

-   -   generating 310′ an irradiation control signal by an irradiation        control system 110′;    -   generating 320′ an irradiation by an irradiation source 120′,        coupled to the irradiation control system 110′;    -   receiving 330′ the irradiation and delivering 332′ a patterned        irradiation to an iris of the eye with an irradiation delivery        system 130′; and    -   controlling 340′ at least one of the irradiation source 120′ and        the irradiation delivery system 130′ by the irradiation control        signal of the irradiation control system 110′ so that the        patterned irradiation causes a long-term constriction of the        pupil of the eye.

In the method 300′, the causing the long-term constriction of the pupilcan include increasing a temperature of a treatment region of the iristo a range of 50-80 degrees Celsius. In some cases, the method 300′ caninclude increasing a temperature of the treatment region of the iris toa range of 55-70 degrees Celsius. While these ranges have some overlapwith temperature ranges described in relation to the temporarystimulator 100, for a particular patient the temperature range where theconstriction is temporary can be quite well separated from thetemperature range, where the constriction is permanent. For example, fora particular patient, temperatures in the range of 50-55 C may constrictthe pupil for a day or less; temperatures in the 55-60 C range may causethe pupil to constrict for a time between a week and a month,temperatures in the 60-65 C range can cause the pupil to constrict for atime between a month and a year, and temperatures in the 65-70 C rangemay cause the pupil to constrict for a time longer than a year. Theselong-term changes can very well be associated with an irreversiblechange in the iris of the eye.

As before, in some embodiments of the method 300′ the irradiationcontrol system 110′ can include an imaging system 114 and a userinterlace 118; and the generating the irradiation control signal caninclude generating an image of the iris of the eye with the imagingsystem 114 for a user, receiving an image-based input from the userthrough the user interface 118, and generating the irradiation controlsignal to control the irradiation delivery system 130′ to deliver thepatterned irradiation 200 p′ in accordance with the received input.

In some embodiments of the method 300′, the irradiation control system110′ can include an alignment system 135; and the generating theirradiation control signal can include processing alignment data withthe alignment system 135, and generating the irradiation control signalto control the irradiation delivery system 130′ to deliver the patternedirradiation 200 p′ to the iris in a pattern 210 aligned with a pupil ofthe iris.

As discussed, the ophthalmologist operating the stimulator 100′ cananalyze several factors when practicing the method 300′. The analysiscan include the determination what treatment parameters to use toachieve a long-term or permanent constriction change, to go beyond thepreviously described temporal changes. The analysis can also be focusedat which treatment regions to irradiate. As discussed before, somevision-improvement goals can be better achieved by heat-treating theradial dilator muscles 30, others by heat-treating the circularsphincter muscles 40.

Both of these analyses can involve acquiring and analyzing patient data.In a typical example, a patient may have used the temporary ophthalmicstimulator 100 by practicing the method 300 repeatedly and for anextended period, and may have grown comfortable with its effect to thedegree that she/he decided to make the constriction of the pupilpermanent. During these preceding temporary treatments, the irradiationcontroller 110 of the stimulator 100, or its operator may have acquiredand collected a substantial amount of data about the particular patient.An ophthalmologist, who is planning administering a higher energyirradiation by practicing the method 300′ with a permanent ophthalmicstimulator 100′ to permanently change the constriction of the pupil, mayevaluate and analyze the data that was collected during the previous,repeated temporary constrictions of the pupil of this particularpatient. This analysis can be followed by selecting a treatment regionbased on the analyzing of the patient data; and delivering the patternedirradiation 200 p′ to the selected treatment region to cause thelong-term constriction of the pupil.

FIG. 7A illustrates that some embodiments of the ophthalmic stimulator100 may include an irradiation control system 110, to generate anirradiation control signal; a light source 120, coupled to theirradiation control system 110, to generate a light beam 200; and abeam-shaping optics 132, coupled to the irradiation control system 110,to receive the light beam 200 from the light source 120, and to delivera light ring 200 r to an iris 11 of the eye in a ring pattern 210 r. Inembodiments, the irradiation control system 110 can control the lightsource 120, or the beam-shaping optics 132, or both, with theirradiation control signal so that the light ring 200 r causes atemporary constriction of the pupil of the eye, without causing apermanent constriction of the pupil. The beam-shaping optics can alsoinclude an objective 133, to direct the light ring 200 p towards theiris of the eye, to provide additional control.

Embodiments of the here-described ophthalmic stimulator 100 can beanalogous, or equivalent to the embodiments described in relation to thestimulator 100 in relation to FIGS. 5A-B and 6A-D. In particular, theembodiments of the irradiation source 120 can also serve as the lightsource 120 here. For example, the light source can be an infrared lightsource. Also, the beam-shaping optics 132 can be an embodiment of theirradiation delivery system 130.

FIG. 7B illustrates that the beam-shaping optics 132 can include aproximal axicon lens 140, positioned with its base-plane oriented towardthe light source 120, to transform the received light beam 200 into thelight ring 200 r.

Here it is recalled that an axicon lens is a glass cone with a circle asits base. An axicon lens can be also visualized as an isoscelestriangle, rotated around its axis of symmetry. Direct ray tracingestablishes that axicon lenses transform a regular, full light beam intoa light ring 200 r. Generating the light ring 200 r “passively”, withoutany scanners, or other digitally controlled active optics with movingparts, makes an axicon lens a very useful, simple, and reliableimplementation of the beam-shaping optics 132 for the purposes of thestimulator 100.

However, it is also noted that the radius r(ring) of the light ring 200r increases with the distance d(target) from the axicon lens 140.Therefore, if the patient moves her/his head along the optical axis,doing so changes the radius r(ring) of the light ring 200 r and can haveundesirable medical effect.

FIG. 7C illustrates an embodiment of the beam-shaping optics 132 thatresolves this problem. This embodiment includes the proximal axicon lens140-1, with its base-plane oriented towards the light source 120. Itfurther includes a second, distal, “complementary” collimating axiconlens 140-2, that is co-axial with the proximal axicon lens 140-1,positioned with its cone-tip oriented toward a cone-tip of the proximalaxiom lens 140-1, to collimate the light ring with the increasing radiusinto a light ring with a constant radius, independent of the distanced(target).

Embodiments with such a complementary axicon lens pair 140-1 and 140-2can further include a lens position actuator 141, to adjust an axicondistance d(axicon) between the proximal axicon lens 140-1 and the distalaxicon lens 140-2. Changing the axiom distance d(axicon) can be used toadjust the radius r(ring) of the light ring 210 as part of the settingof the overall ring pattern 210 by the ophthalmic surgeon in FIGS.12D-E.

Additional optical solutions may be needed to tune Rp(inner)independently from Rp(outer), to tune the radius of the ringindependently from its width. Examples of such solutions include (a) abeam blocker to block out part of the light ring; (b) a deformableaxicon lens 140, capable of changing the angle of the cone of the axiconlens; and (c) a deformable mirror, in some cases a deformable conicalmirror.

An important aspect of ophthalmic irradiation systems is to ensure thatthe patient's eye is aligned with the optical axis of the irradiationsystem. Previously, various alignment systems 135 have been alreadydescribed. A particularly useful element of such alignment systems 135can be a fixation light 202, as mentioned. The surgeon may instruct thepatient to stare, or fixate, on a centrally positioned fixation light.Such fixation lights 202 can be provided by a small bright LED,positioned centrally, projected into, or superimposed into the opticalpathway.

FIG. 7D shows that the beam-shaping optics 132 that uses an axicon lens140 offers a particularly simple implementation of the fixation light202. In some embodiments, the tip of the cone of the axicon lens 140 maybe flattened. Such flattened tip axicon lenses 140 do not redirect orrefract the small central portion of the incoming light 200, so thatthey propagate centrally and thus can act as the fixation light 202.Such embodiments are attractive because the fixation light 202 isnaturally centered with the beam-shaping optics 132, without the need tointroduce any additional structures to hold the fixation light in placethat can at the same time block part of the light 200, and without theneed of centering the fixation light 202 by a finely adjustable system.

In the case when the treatment light 200 is an infrared light, theflattened tip can be covered by a luminescent material, a phosphor, anupconverting material, a higher harmonic generating material, amulti-photon induced fluorescence material, or any optical material orstructure that converts the infrared light 200 into a visible light,needed as a fixation light 202.

FIG. 7E illustrates an embodiment of the beam-shaping optics 132. Theincoming light 200 can be guided through a pair of beam-expandinglenses: a diverging, lens 142, followed by a collimating lens 143. This142-143 lens combination can expand the radius of the incoming beam 200to the Rp(outer) outer radius, set or desired by the ophthalmic surgeon.The beam radius can be adjusted by adjusting the distance of thediverging lens 142 from the collimating lens 143 by an actuator. Next,the expanded beam can be directed at an adjustable beam stop 144 thatcan block out a central portion of the expanded beam so that thetransmitted beam has an inner radius equaling Rp(inner) as set by thesurgeon. The radius of the adjustable beam stop 144 can be adjusted by anumber of known mechanical designs. Further, since the stopped beamcarries an energy with it that can undesirably heat the beam-shapingoptics 132, a heat sink 145 can be employed, configured to absorb, orguide away the energy of the stopped beam. Many heat sinks are known,such as metallic ribs, and air-cooled systems. It is also possible toreflect the stopped beam out of the beam-shaping optics 132 and absorbit or release it peripherally. These solutions reduce the need for heatmanagement greatly.

FIG. 7F illustrates another embodiment of the beam-shaping optic 132.This embodiment 132 can be configured to generate a light beam directlywith a ring shape, without the need of an optics that would transformthe generated light. In a typical embodiment, the light source 200 caninclude a ring of LEDs 146-1, 146-2, . . . 146-N, collectivelyreferenced as 146-i, to generate light beamlets; and a ring-shapeddiffuser 147, to transform the light beamlets into a light beam with awell-distributed intensity profile to form the light ring 200 r. In someembodiments, there can be more than one ring of LEDs 146-i. Activating adifferent number of LED rings can be one way to adjust the radius of thelight ring 200 r. (Throughout this document, elements “x-1, x-2, . . . ,x-N” will be sometimes collectively referenced as “x-i”, for brevity.)

Finally, the embodiments of FIGS. 7B-F can be combined. One suchcombination was already mentioned. The embodiment based on theaxicon-lens 140, or 140-1/140-2, may need additional optical elements toadjust the inner and outer radii Rp(inner) and Rp(outer) independently.In some cases, the beam stop 144 can be used to adjust the inner radiusRp(inner) of the light ring 200 r that was generated by the axicon lens140.

FIG. 11C illustrates a method 302 for temporarily constricting a pupilof an eye by an ophthalmic stimulator 100. The method 302 can includethe following steps:

-   -   generating 302 a an irradiation control signal by an irradiation        control system 110;    -   generating 302 b a light beam 200 by a light source 120, coupled        to the irradiation control system 110;    -   receiving 302 c the light beam 200, and delivering 302 d a light        ring 200 r to an iris of the eye with a beam-Shaping optics 132;        and    -   controlling 302 e at least one of the light source 120 and the        beam-shaping optics 132 by the irradiation control signal of the        irradiation control system 110 so that the light ring 200 r is        causing a temporary constriction of the pupil of the eye,        without causing a permanent constriction of the pupil.

In some embodiments of the method 302, the delivering 302 d the lightring 200 r can include transforming the received light beam 200 into thelight ring 200 r by a proximal axicon lens 140, positioned with itsbase-plane oriented toward the light source 120, wherein the light ring200 r has an increasing radius r(ring) with increasing distanced(target) from the axicon lens 140.

In some cases, the delivering 302 d the light ring 200 r can includecollimating the light ring with the increasing radius into a light ring200 r with a constant radius by a distal collimating axicon lens 140-2,co-axial with the proximal axicon lens 140-1, positioned with itscone-tip oriented toward a cone-tip of the proximal axicon lens 140-1.In these embodiments, the delivering the light ring can includeadjusting an axicon distance d(axicon) between the proximal axicon lens140-1 and the distal axicon lens 140-2 by a lens position actuator 141,thereby adjusting the radius of the light ring, r(ring).

The method 302 can also include generating a fixation light 202 byselectively transmitting a small fraction of the received light beam 200by a flattened cone-tip of the proximal axicon lens 140-1. Inembodiments where the light is an infrared light, the small, flattenedtip of the axicon lens 140-1 can be covered by an optical material thatcan transform the infrared light into a visible light.

In some embodiments of the method 302, the delivering 302 d the lightring can include utilizing a beam stop 144 to generate the light ring200 r by blocking a central portion of the received light beam 200.

Finally, in some embodiments of the method 302, the generating 302 b alight beam can include generating the light beam with a ring shape bythe light source including a ring of LEDs 146-i.

FIG. 8A illustrates that embodiments of the ophthalmic stimulator 100for temporarily constricting a pupil of an eye can include a digitalbeam controller 110, to generate a digital beam-control signal; a lightsource 120, coupled to the digital beam controller 110, to generate alight beam 200; and a digitally controlled beam modulator 134, forexample a beam scanner 134, to receive the digital beam-control signalfrom the digital beam controller 110, to receive the light beam from thelight source 120, and to modulate the received light beam into amodulated light, or modulated light 200 m, delivered to an iris of theeye. In embodiments, the digital beam controller 110 can control thelight source 120, the digitally controlled beam modulator 134, or both,with the digital beam-control signal so that the modulated light 200 mcauses a temporary constriction of the pupil of the eye, without causinga permanent constriction of the pupil.

As before, embodiments of the here-described ophthalmic stimulator 100can be analogous, or equivalent to the embodiments described in relationto the ophthalmic stimulator 100 in relation to FIGS. 5A-B, 6A-D, and7A-F. In particular, the embodiments of the irradiation control system110 can be analogous, or equivalent, to the embodiments of the digitalbeam controller 110, the irradiation source 120 can also serve as thelight source 120 here, and the digitally controlled beam controller 134can be an embodiment of the irradiation delivery system 130.

In what follows, numerous examples of the digitally controlled beammodulator 134 will be described. To emphasize that all these areembodiments of the same block, they are all labeled with 134 or as avariant of label 134.

For example, FIG. 8A illustrates a beam scanner 134 as an embodiment ofthe digitally controlled beam modulator 134, to scan the received lightbeam 200 according to a pattern 210 on the iris. Embodiments describedin relation to FIGS. 8A-B, and FIGS. 9A-E can be different from theembodiments described in relation to FIGS. 7A-F in that the latterembodiments utilize dominantly “passive” optical elements, such aslenses and mirrors, and do not need elaborate digital control signalsand moving parts, with the possible exception of the lens positionactuator 141. Also, the systems of FIGS. 7A-F typically irradiate thepattern 210 simultaneously.

In contrast, the digitally controlled embodiments of FIGS. 8A-B, andFIGS. 9A-E can involve active elements, where extensive digital controlsignals move or adjust a number of active optical elements. Theseembodiments typically irradiate the iris on a point-by-point basis, withthe help of various types of scanners and optical arrays. As such, thesedigitally controlled embodiments can offer higher precision and control,at the same time, they can be more complex, raising issues ofreliability, maintenance and costs, and the irradiation treatment cantake longer. Also, the points of the pattern 210 are often irradiatedsequentially, instead of simultaneously.

FIG. 8B illustrates one embodiment of the digitally controlled beammodulator 134 in a laser-based ophthalmic stimulator 100. The lightsource 120 can be a laser source 120L, emitting a laser beam 200L. Thedigitally controlled beam modulator 134 can be an X-Y scanner 134L, toscan the received laser beam 200L as a scanned laser beam 200 sLaccording to a pattern on the iris. A large number of laser scanners areknown that can scan the scanned laser beam 200 sL with a wide variety ofcomplex patterns 210.

FIG. 9A illustrates the first of a set of reflection mode beammodulators 134 r. While the scanner embodiments in FIGS. 8A-B irradiatethe iris in a pattern 210 sequentially, the embodiments of FIGS. 9A-Ecan irradiate the pattern 210 either sequentially, or simultaneously.The embodiment of FIG. 9A includes a reflective LCD array 150 with anaddressable array of LCD pixels 152. Switching the LCD pixels 152 on-offcan control how much of an incoming light the LCD array reflects fromthrough the LCD pixels.

FIG. 9B illustrates another embodiment of the reflection-mode beammodulator 134 r that includes a deformable reflector 160, with asubstrate 162; a mechanical actuator array 164, positioned on thesubstrate 162; and a deformable mirror 166, positioned to be deformableby the mechanical actuator array 164 according to the digitalbeam-control signal.

FIG. 9C illustrates yet another embodiment of a reflection-mode beammodulator 134 r. This is an acousto-optical modulator 170 that includesa set of acoustic piezo transducers 172, to deform a deformablereflector 174, according to the beam-control signal. This embodiment hassimilarities to the previous one in FIG. 9B. One of the differences isthat the deformation is performed not by an array that can be controlledpoint-by-point, but in a global manner, where the transducers areoperated to form patterns across the entire deformable reflector 174simultaneously.

FIG. 9D illustrates yet another embodiment of a reflection-mode beammodulator 134 r. This is a digital mirror device 180 that includes asubstrate 182; an array of mechanical actuators 184-i, positioned on thesubstrate 182; and an array of rotatable mirrors 186-i, where therotatable mirrors 186-i are rotatable individually by the actuators184-i according to the beam-control signal. Such digital mirror arraysare well known in digital projectors, for example.

FIG. 9E illustrates a different, transmission-mode beam modulator 134 t.This embodiment can include an addressable pixel array 190 of variabletransparency pixels 192-i. This embodiment 190 has design aspectsanalogous to the embodiment 150 in FIG. 9A, as it also builds on theprinciple of individual pixels changing their optical (reflective ortransmissive) properties under electric, control, thereby modulating thebeam on a pixel-by-pixel basis. As indicated earlier, the irradiationcan be either sequential or in parallel, the latter type embodimentsrequiring much less moving parts and allowing shorter irradiation times.

FIGS. 17A-D illustrate various patterns 210 the digitally controlledophthalmic stimulators 100 can irradiate on the iris with the modulatedbeam 200 m. In embodiments, illustrated in FIG. 17A, the digitallycontrolled beam modulator 134 can be controlled by the beam controller110 to modulate the received light beam 200 into a modulated light 200m, so that it irradiates a pattern 210 that is a ring, or multiplerings. FIG. 17B illustrates a pattern 210 that is a segmented ring. FIG.17C illustrates a pattern 210 that includes radial spokes. Finally, FIG.17D illustrates a pattern that is a combination of ring segments andspokes.

FIG. 11D illustrates a method 304 that is related to operating thedigitally controlled ophthalmic stimulators 100. The method 304 caninclude the following steps:

-   -   generating 304 a a digital beam-control signal by a digital beam        controller 110;    -   generating 304 b a light beam 200 by a light source 120, coupled        to the digital beam controller 110;    -   receiving 304 c the light beam 200, modulating 304 d the light        beam 200 into a modulated light 200 m, and delivering 304 e the        modulated light 200 m to an iris of the eye, with a digitally        controlled beam modulator 134; and    -   controlling 304 f the light source 110, the digitally controlled        beam modulator 134, or both, by the digital beam-control signal        of the digital beam controller 110 so that the modulated light        200 m is causing a temporary constriction of the pupil of the        eye, without causing a permanent constriction of the pupil.

In embodiments, the modulating 304 d can include scanning the receivedlight beam on the iris according to a pattern by a beam scanner 134. Inother embodiments, the modulating 304 d can include modulating the lightby a reflection-mode beam modulator 134 r. The reflection-mode beammodulator 134 r can be a reflective LCD array 150, with an addressablearray of LCD pixels, a deformable reflector 160, an acousto-opticalmodulator 170, and a digital mirror device 180. In some embodiments ofthe method, the modulating 304 d can include modulating the light by atransmission-mode beam modulator 134 t.

Finally, the modulating 304 d can include modulating the received lightbeam into the modulated light 200 m with the pattern being one of aring, multiple rings, a segmented ring, a pattern of radial spokes, anda combination of ring segments and spokes.

FIG. 15 illustrates other embodiments of an ophthalmic stimulator 100for temporarily constricting a pupil of an eye that includes anirradiation control system 110, having a feedback system, to generate anirradiation control signal using a feedback of the feedback system; anirradiation source 120, coupled to the irradiation control system 110,to generate an irradiation; and an irradiation delivery system 130,coupled to the irradiation control system 110, to receive theirradiation 200 from the irradiation source 120, and to direct apatterned irradiation 200 p in a pattern to a treatment region of aniris of the eye, guided by the feedback-based irradiation controlsignal; wherein the irradiation control system 110 controls at least oneof the irradiation source 120 and the irradiation delivery system 130with the feedback-based irradiation control signal so that the patternedirradiation 200 p causes a temporary constriction of the pupil, withoutcausing a permanent constriction of the pupil. As before, thehere-described embodiments can be analogous to the ones described inrelation to FIGS. 5A-B, FIGS. 6A-D, FIGS. 7A-F, and FIGS. 8A-B, andanalogously labeled elements can serve analogous functions.

In what follows, various embodiments and blocks of the feedback system116 will be described. These embodiments and blocks typically include ahardware block, such as an imaging system, or a temperature sensor. Theyare coupled to the irradiation controller 112, which processes theirfeedback and generates irradiation control signals, to be transmitted tothe irradiation source 120 and to the irradiation delivery system 130.As discussed in relation to FIG. 10, the irradiation controller 112 caninclude corresponding blocks that are dedicated to receive the feedback.For example, the irradiation controller 112 can include the dedicatedfeedback block 112 a to receive the feedback from an embodiment of thefeedback system 116. These receiving blocks can be implemented inhardware, such as an application specific integrated circuit ASIC; orthey can be implemented in a software form, such as a piece of code orapplication, implemented in the processor 113 of the irradiationcontroller 112; or in a shared processor, or input/output controller. Inyet other embodiments, the feedback can be coupled straight into thecentral processor 113, whose code can process the feedback directly. Aparticularly simple implementation can be a simple “stop” feedbacksignal, triggered by a security concern, which can be directly executedby the processor by shutting down the irradiation source 120 with acontrol signal, without the need of any intermediate processing.

In some embodiments, the feedback system 116 can include at least one ofa pupillometer 116 a and an imaging system 114, to sense a diameter ofthe pupil, and to generate a feedback according to the sensed pupildiameter. As discussed just now, this feedback can be received andprocessed either by a dedicated feedback block 112 a that is implementedinside the irradiation controller 112, or can be received by theprocessor 113 of the irradiation controller 112 itself. In someembodiments, the pupillometer 116 a can be coupled to the irradiationcontroller 112 directly, in others, through a user interface 118-1 a.Similarly, the imaging system 114 can be coupled to the irradiationcontroller 112 directly, or through a user interface 118-2.

FIGS. 16A-E illustrate methods, or processes, 510-550 that operate inrelation to the embodiments 116 a-f of the feedback system 116. Ingeneral, the methods, or processes, 510-550 can include the followingsteps:

-   -   generating a feedback-based irradiation control signal by an        irradiation control system 110, using a feedback of a feedback        system of the irradiation control system;    -   generating an irradiation 200 by an irradiation source 120,        coupled to the irradiation control system;    -   receiving the irradiation 200 and directing a patterned        irradiation 200 p to a treatment region of an iris of the eye        with an irradiation delivery system 130, guided by the        feedback-based irradiation-control signal; and    -   controlling at least one of the irradiation source 120 and the        irradiation delivery system 130 with the feedback-based        irradiation control signal of the irradiation control system 110        so that the patterned irradiation 200 p causes a temporary        constriction of the pupil, without causing a permanent        constriction of the pupil.

The description continues with details of the processes, or methods,510-550. FIG. 16A illustrates that in a representative case, thefeedback can be generated through the following sequence, method, orprocess 510. A short time after starting to apply the patternedirradiation 200 p to the iris 11 according to the pattern 210, in step511, the pupillometer 116 a, or the imaging system 114, can sense that“Pupil radius is large relative to a reference or target”, or “Targetradius not reached”. This can be followed by a step 512, generating thefeedback, or feedback signal: “Carry on irradiation”, as indicated bythe eye and steps on the left side of FIG. 16A. Here and in whatfollows, each “step x of generating feedback signal” may also bereferred to with the shorter form of “feedback signal x”, for brevity.Also, the feedback signal can include not only the command to continueor to stop the irradiation, but it can also include the sensedinformation as well. In the present example, the step 512 of generatinga feedback signal can include sending the feedback signal “Target radiusnot reached. Carry on.”

With the passing of time, the irradiation increases the temperature of aportion of the iris 11, as indicated by the denser dot-filling of thepattern 210 on the right. The increased temperature induces theconstriction of the pupil 13, as indicated by the eye 1 having a smallerpupil 13 on the right of FIG. 16A. In step 513, the pupillometer 116 a,or the imaging system 114, can sense that “Pupil radius is sufficientlyclose to the reference”, or “Target pupil radius sensed”, This can befollowed by the generation of the feedback in step 514: “Power downirradiation”, or “Target radius reached. Power down”. This feedback, orfeedback signal 514 can be transmitted by the feedback system 116 to theirradiation controller 112. In response, the irradiation control system110 can send a corresponding feedback-based irradiation control signalto the irradiation source 120 to power down. The top graph of FIG. 16Aillustrates that the feedback-induced irradiation control signal 514causes the powering down of the irradiation after the receiving of thefeedback signal 514.

It is mentioned here that pupillometers reached a high level ofsophistication and can provide a variety of useful, actionableinformation. For a review of the field, see Olson D, Stutzman S, Saju C,Wilson M, Zhao, W., Aiyagari V. Interrater of Papillary Assessments,Neurocrit Care, Published online: 17 Sep. 2015. These pupillometers canassess pupil size, and shape with very high accuracy andreproducibility. In addition, such devices can measure parameters suchas onset and peak constriction, constriction and dilation velocity, andlatency using various light stimuli, both before and after treatment toassess effects that may not be apparent simply based on pupil diameter.

FIG. 15 illustrates that in some embodiments, the feedback system 116can include a pupillometer 116 a, and at least one of an infrared sensoror camera 116 b to sense a temperature of the treatment region, and togenerate a feedback according to the sensed temperature. As before, theinfrared camera 116 b can be coupled to the irradiation controller 112directly, or via a user interface 118-1 b.

FIG. 16B illustrates the corresponding process 520, or method 520, orsequence of operation of this infrared sensor/camera 116 b. At an earlytime during the irradiation, in a step 521, the infrared sensor/camera116 b can sense “Temperature low relative to a reference”, or simply“Low temperature”. In a typical case, a temperature T sensed to be lessthan 45 C can be classified as “low temperature”. This can promptgenerating the feedback in step 522: “Carry on irradiation”. Visiblythis feedback leads to the maintaining the power of the irradiation, asindicated by the graph on top of FIG. 16B.

With the progression of the irradiation time, the target region,irradiated according to the pattern 210, starts warming up. This isindicated by the dotting of the pattern 210 getting denser. After sometime, in step 523, the infrared (thermal) sensor/camera 116 b can sense“a medium temperature relative to the reference”, or simply “mediumtemperature”. In a typical example, this can be a temperature in the 45C-55 C range. In response, a feedback signal can be generated in step524, sent from the feedback system 116 to the irradiation controller112: “Start power down the irradiation”, or “Medium temperature. Powerdown”. As indicated, the irradiation control system 110 can generate afeedback-based irradiation control signal to the irradiation source 120,which is response can start powering down the power of the irradiationgradually, as indicated by the dashed line in the top graph.

In some embodiments, the settings and thresholds can be chosendifferently. In such cases, the IR camera 116 b can wait until it sensesa “high temperature relative to the reference” in step 525, such as theIR sensor/camera 116 b senses the temperature T that exceeds 55 C. Sucha sensing by the IR sensor/camera 16 b can prompt the generation of thefeedback “Stop the irradiation” in step 526, to be sent to theirradiation controller 112. Analogously to earlier steps of the process,the irradiation control system 110 can generate a feedback-basedirradiation control signal for the irradiation source 120 to discontinuethe irradiation with a hard stop, as indicated by the solid line in thetop graph of FIG. 16B.

One such scenario can be associated with an irregular, or unexpectedprogress of the irradiation, when, for whatever reason, the iris heatsfaster than expected. This can be a consequence of an unexpected patientresponse, or an incorrect calibration of the irradiation's treatmentparameters. Once the IR camera 116 b senses that the temperature rose toa value high relative to a reference, such as to above 55 C, for safetyreasons the feedback-based irradiation control signal can bring theirradiation power to zero via a hard stop.

FIG. 15 illustrates that the feedback system 116 can further include atleast one of an alignment system 116 c, an eye tracker 116 d, awavefront sensor 116 e, an iris scanner 116 f, and an imaging system114. The alignment system 116 c can be related to, combined with, oranalogous to any embodiment of the alignment system 135, describedearlier, for example in relation to FIGS. 12A-C. Any of these feedbackimplementations can sense an alignment of one of the iris and the pupilrelative to the irradiation delivery system 130, as discussed earlier.

FIG. 16C illustrates a mode of operation, or method 530 for suchalignment-related feedback implementations. While FIG. 16C specificallyrefers to the eye tracker feedback 116 d, an analogous process can bepracticed with the analogous feedback alignment system 116 c, irisscanner 116 f, or imaging system 114. In a step 531, the eye tracker 116d can “sense alignment” between the iris 11, the pupil 13 and theirradiation delivery system 130. Sensing alignment in step 531 can leadto generating, in step 532, the feedback “Eye aligned. Carry onirradiation”, which results in the irradiation source 120 maintainingthe power of the irradiation, as shown by the top graph of FIG. 16C.

A central concern for the efficacy and safety of the irradiationtreatment is that the eye 1, iris 11, and pupil 13 remain aligned withthe irradiation delivery system throughout the irradiation. However,there is a possibility that the eye, iris, and pupil become misaligned.This can be caused by an involuntary eye movement by the patient, areaction to a sensation of discomfort or pain by the patient, or aproblem developing with the patient interface 137, such as the breakingof a vacuum suction, among others. Also, misalignment can be the naturalconsequence of the ophthalmologist not using a firm eye-fixation method,such as physically restraining the eyeball only by hand, or by pressurewith a forceps. In these cases, the gaze of the eye can naturally driftaway to a degree that it becomes misaligned with the pattern 210 and theirradiation delivery system 130.

FIG. 16C illustrates that the eye can get misaligned to a degree thatthe patterned irradiation 200 p may reach the edge of the pupil 13. Insuch cases, the irradiation may start hitting the retina, a much morelight-sensitive tissue. This raises a higher level of safety concerns.Embodiments of the feedback system 116 can handle such developments bythe eye tracker 116 d “sensing a misalignment”, or “misalignment sensed”in step 533. This can lead to a generation of a feedback signal “Eyemisaligned! Safety Stop!” in step 534. The irradiation control system110 can generate a corresponding feedback-based irradiation controlsignal for the irradiation source 120, which in response can execute ahard stop of the irradiation, as shown by the top graph. The step 534can be accompanied with a signal to an operator, or user: “Realign atleast one of the irradiation delivery system, the iris, and the pupil.”

FIG. 16D illustrates a process, or method 540 that flexibly managesnaturally occurring misalignments. Steps 541-544 are analogous to steps531-534, in relation to the eye losing alignment with the irradiationdelivery system 120. However, the process 540 can dynamically manage ifthe misalignment developed not as a safety-threatening problem thatrequired an irreversible hard stop, but as a consequence of a naturallyshifting eye, which can be followed by the eye realigning with theirradiation delivery system 130. A typical situation can be when the eyeis not docked to the ophthalmic stimulator 100 in a fixed manner with apatient interface 137, but is left free. In such embodiments, thepatient may be fixating on a fixation light, but her gaze can bedistracted for a short period by natural processes such as a milddiscomfort or blinking, after which the patient re-fixates on thefixation light, thus realigning the eye with the irradiation deliverysystem 130. Such scenarios can be managed by the process 540 via step545, where the eye tracker 116 d can “sense a realignment”, followed bystep 546, where a feedback signal is generated confirming “Eyerealigned. Resume irradiation”. The irradiation control system 110 canthen generate a feedback-based irradiation control signal that makes theirradiation source 120 to resume the irradiation.

In some cases, the “stop irradiation 544—resume irradiation 546”sequence can be repeated several times. A notable embodiment can be ahand-held, mobile ophthalmic stimulator 100 m, described below inrelation to FIGS. 13A-C, where the eye can fall out from alignmentrelative to the irradiation delivery system 130 m repeatedly, followedby the eye getting realigned with the irradiation delivery system 130 mof the mobile ophthalmic stimulator 100 m repeatedly, since the eyes ofthe patient are not held firmly in place by an immobilizing system.

Finally, FIG. 16E illustrates yet another feedback method or process550. In this method, or process, 550, the feedback system 116 caninclude at least one of the pupillometer 116 a and the imaging system114, to sense at least one of a pupil characteristic or an irischaracteristic, and to generate a feedback according to the sensedcharacteristic.

In step 551, the imaging system 114 may sense that the pupil 13 has aregular shape. In response, it may generate the feedback signal:“Progress regular. Carry on,” in step 552. However, in some cases, instep 553 the imaging system 114 may sense, or image, that an “irregularpupil shape” is emerging as a consequence of the irradiation. In otherembodiments, the imaging system 114 may sense, or image, that at leastone of a pupil characteristic and an iris characteristic is becomingunacceptable relative to a reference as a consequence of theirradiation. These situations can arise, when the pupil does not reactaccording to medical expectations to the irradiation. A simple examplecan be that the pupil starts to lose its circular shape, and evolvetoward an elongated, or irregular shape. A non-circular pupil can beperceived as an undesirable treatment outcome and therefore necessitatessafety protocols within the feedback system 116 to manage or tocounter-act it.

A corresponding step 554 can include the generation of a “modifyirradiation pattern” feedback signal, possibly preceded by a “safetystop” feedback signal 554. The process 550 can be continued by thepattern generator 112 e actually modifying the irradiation pattern 210in step 555, followed by generating a “Pattern modified. Resumeirradiation,” feedback 556.

FIG. 16E illustrates a characteristic example, where the pupil 13 startsto evolve from circular towards an elongated oval shape because of theirradiation. This undesirable process can be detected by the imagingsystem 114 in step 553. In response to the corresponding, feedback-basedirradiation control signal, the irradiation delivery system 130 maychange the irradiation pattern 210 from a circle into an oval that isoriented 90 degree opposite to the pupil's oval. Such a modifiedirradiation pattern 210 p may be successful to counter-act thedevelopment of the undesirable oval pupil.

Irradiation delivery systems 130 and 134 that are digitally controlledand active systems, like the beam modulators and beam scanners 134 ofFIGS. 8A-B, and the digitally controlled beam modulators 134 of FIGS.9A-E, can modify the irradiation patterns 210 relatively easily. Thebeam-shaping optics 132 of the optical systems in FIGS. 7A-F with littleor no digital, point-by-point control can also have some suchfunctionalities. A simple embodiment can be the beam-shaping optics 132including deformable mirrors. Actuators along the periphery, or alongthe perimeter of such deformable mirrors can elongate a circular pattern210 into an oval pattern 210 by a simple cylindrical deformation of themirror. Other low order wavefront deformations can be also introduced bydeforming such a deformable mirror. Such deformable mirrors were alsodescribed earlier as systems that can enable the independent tuning ofthe Rp(inner) and the Rp(outer) radii of the pattern 210, and also inrelation to FIGS. 9B-C.

Further embodiments can include further methods or processes, where thefeedback system 116 includes the wavefront sensor 116 e, or the irisscanner 116 f, and the method includes generating a feedback based on acondition of at least one of the iris and the pupil, sensed by thewavefront sensor 116 e, or the iris scanner 116 f.

In yet other embodiments, the feedback system 116 can be configured tocarry out a test and then generate a feedback signal based on the test.In a simple embodiment, during the treatment, a short light pulse can besent to the eye, and the reaction time, or the reaction radius-change ofthe pupil can be measured and assessed by the feedback system 116. Afeedback-based irradiation control signal can then be generated based onthis assessment.

In some cases, the feedback by the feedback system 116 can serve only adiagnostic purpose, not necessarily leading to the generation of afeedback signal to impact the irradiation. This feedback can be a visualfeedback for the operator, or user of the ophthalmic stimulator 100 viaa user interface 118-1 a to 118-1 f or 118-2. The user may, in responseto this visual feedback, then modify the treatment. The feedback can bea wide variety of information, from pupil size to sensed temperature, toa pupil shape or alignment.

In some embodiments, an ophthalmic stimulator 100 for constricting thepupil 13 of an eye 1 can include an irradiation control system 110,having a safety feedback system 116, to generate a feedback-basedirradiation control signal using a feedback of the safety feedbacksystem 116; an irradiation source 120, coupled to the irradiationcontrol system 110, to generate an irradiation 200; and an irradiationdelivery system 130, coupled to the irradiation control system 110, toreceive the irradiation 200 from the irradiation source 120, and todirect a patterned irradiation 200 p in a pattern 210 to a treatmentregion of an iris 11 of the eye 1, guided by the feedback-basedirradiation control signal. In these embodiments, the irradiationcontrol system 110 can control at least one of the irradiation source120 and the irradiation delivery system 130 with the feedback-basedirradiation control signal so that the patterned irradiation 200 pcauses a long-term constriction of the pupil 13.

Including the safety feedback system 116 can be critically important toguarantee the safety of the operation of the ophthalmic stimulators 100,especially those that are powerful enough to cause a long-termconstriction of the pupil 13. In the here-described embodiments, thesafety feedback systems 116 are safety-oriented feedback systems, whoserole can be critically different from simple guiding or aligningfeedback systems which may only help the targeting of the irradiation,but are not part of ensuring the safety of the irradiation. Variousembodiments of the safety feedback system 116 can provide feedback whenthe desired result has been achieved, as determined from a pupil sizemeasurement, for example. This feedback ensures the safety of thetreatment by signaling that further irradiation is not necessary and infact may be harmful. In other embodiments, a feedback can be generatedby the safety feedback system 116 if a misalignment has been detected,and the irradiation by the laser source 120L may be inadvertentlydirected at the retina of the eye 1. Yet other examples includegenerating a feedback to indicate that a temperature of the targettissue rose to a reference level, or exceeded a critical level. In theseembodiments, the feedback of the safety feedback system 116 can indicatethat the treatment goal has been achieved, or the possibility of anundesirable medical outcome, such as retinal exposure, or overheatingthe iris tissue. Receiving such a feedback from the safety feedbacksystem 116 can prompt the irradiation control system 110 to generate afeedback-based irradiation control signal to stop, or to power down theirradiation. Employing such a safety feedback system 116 can ensure thatthe irradiation is stopped when the treatment goal is achieved, or whenthere is a possibility of an undesirable medical outcome. As such,including the safety feedback system 116 into the ophthalmic stimulator100 can be critical to ensure its safe operation.

FIG. 15 illustrates that in some embodiments of the ophthalmicstimulator 100 the safety feedback system 116 can include at least oneof a pupillometer 116 a and an imaging system 114, to sense a diameterof the pupil, and to generate a feedback according to the sensed pupildiameter. The generated feedback can include at least one of “pupilradius is large relative to a reference, carry on irradiation”; and“pupil radius is sufficiently close to the reference, power downirradiation”.

In some embodiments of the ophthalmic stimulator 100, the safetyfeedback system 116 can include at least one of an infrared camera and athermal sensor 116 b, to sense a temperature of the treatment region,and to generate a feedback according to the sensed temperature. Thefeedback can include at least one of “sensed temperature is low relativeto a reference, carry on irradiation”; “sensed temperature is mediumrelative to the reference, start power down of irradiation”; and “sensedtemperature is high relative to the reference, stop irradiation”.

In some embodiments of the ophthalmic stimulator 100, the safetyfeedback system 116 can include at least one of an alignment system 116c, an eye tracker 116 d, an iris scanner 116 f, and an imaging system114, to sense an alignment of one of the iris 11 and the pupil 13 withthe irradiation delivery system 130. The feedback can include at leastone of: “the irradiation delivery system is aligned with one of the irisand the pupil, carry on irradiation”; and “the irradiation deliverysystem is misaligned with one of the iris and the pupil, stopirradiation, and realign at least one of the irradiation deliverysystem, the iris, and the pupil”.

With reference to FIG. 8B, in some embodiments of the ophthalmicstimulator 100, the irradiation source 120 can include a laser source120L that can be a continuous wave laser, a pulsed laser, or a scannedlaser. A wide variety of laser sources are known in the art that areuseful for ophthalmic applications and can be employed as theirradiation laser source 120L. In particular, femtosecond lasers, withpulse length of 1-1,000 femtosecond and frequencies of 1 kHz.1 MHz havebeen widely used in the art, and can be used for the laser source 120.Other lasers with longer pulse lengths, in the picosecond or evennanosecond range can be utilized as well.

In some embodiments of the ophthalmic stimulator 100, the irradiationsource 120, the irradiation delivery system 130, and the irradiationcontrol system 110 can be configured so that the patterned irradiationcausing the long-term constriction of the pupil includes cauterizingiris tissue. Such embodiments can cause permanent alteration of the iristissue, and therefore can cause permanent shrinking of the pupil.

FIGS. 13A-C illustrate a class of mobile implementations of theophthalmic stimulator 100 m, indicated by the label “m”. Some of theseembodiments will be referred to as a mobile ophthalmic stimulator 100 m.FIG. 13A illustrates that this class of embodiments can include a mobileirradiation control system 110 m, to generate an irradiation controlsignal; an irradiation source 120 m coupled to the mobile irradiationcontrol system 110 m, to generate an irradiation 200; and an irradiationdelivery system 130 m, coupled to the mobile irradiation control system110 m, to receive the irradiation from the mobile irradiation source 120m, and to deliver a patterned irradiation 200 p to an iris of the eye.In embodiments, the mobile irradiation control system 110 m can controlat least one of the irradiation source 120 m and the irradiationdelivery system 130 m with the irradiation control signal so that thepatterned irradiation 200 p causes a temporary constriction of the pupilof the eye, without causing a permanent constriction of the pupil.

In embodiments, the mobile irradiation control system 110 m can includea mobile communication platform 111 m, or simply mobile platform 111 mthat can be a mobile telephone 111 m, a mobile communication device, anda mobile tablet; and a mobile irradiation controller 110 cm, installedon the mobile communication platform 111 m, to generate the irradiationcontrol signal. In a characteristic embodiment, the mobile irradiationcontroller 110 cm can be a software application, downloaded from aprovider over the internet and installed or implemented on a mobilephone 111 m. In other embodiments, the mobile irradiation controller 110cm can be a dedicated processor, for example, in a separate box that canbe installed on the mobile communication platform 111 m by plugging itinto the mobile communication platform 111 m through a USB port,headphone jack, or charging port. For brevity, the mobile irradiationcontroller 110 cm is sometimes simply referred to as irradiationcontroller 110 cm, where the “m” label indicates the mobile nature ofthis irradiation controller. The mobile phone 111 m itself then can beattached to the remainder of the mobile ophthalmic stimulator 100 m,which can be a table-top system that includes the mobile irradiationsource 120 m, and the mobile irradiation delivery system 130 m,installed either in an office of an ophthalmologists, or in a user'sresidence. In some embodiments, the mobile phone 111 m can be coupled tothe rest of the ophthalmic stimulator 100 m by an electric connector ordocking station. In other embodiments, the coupling and communicationbetween the mobile phone 111 m and the rest of the ophthalmic stimulator100 m can be a wireless communication, for example through a Bluetooth,or a wi-fi system or channel.

The mobile communication platform 111 m can include a memory, to storethe above mentioned software implementation of the mobile irradiationcontroller 110 cm; a processor, to execute the stored softwareimplementation of the mobile irradiation controller 110 cm; and a userinterface, to receive input from a user in relation to an operation ofthe memory and the processor.

Once the mobile platform 111 m or mobile phone 111 m is coupled to therest of the mobile ophthalmic stimulator 100 m, a calibration processcan be carried out, so that the mobile irradiation control system 110 macquires information about the type and characteristics of the rest ofthe mobile ophthalmic stimulator 100 m. For example, informationregarding the power and type of the light beam 200 generated by theirradiation source 120 m, and information regarding the type ofsignaling, communication and control protocols needed for thecommunication between the mobile platform 111 m and the rest of themobile ophthalmic stimulator 100 m.

The irradiation delivery system 130 m can include at least one of apattern generator, an optical beam shaper, a patterning optics, a beamprofiler, and a digitally controlled irradiation optics. As in the otherrelated embodiments, the mobile ophthalmic stimulator 100 m can beconfigured to increase a temperature of a treatment region of the iristo a range of 45-60 degrees Celsius.

The mobile irradiation control system 110 m can include a mobile imagingsystem 114 m, such as a mobile camera 114 m, to generate the irradiationcontrol signal by generating an image of the iris of the eye by themobile imaging system 114 m, receiving an image-based input, andgenerating the irradiation control signal to control at least one of theirradiation source 120 m and the irradiation delivery system 130 m todeliver the patterned irradiation according to the received image-basedinput.

In a characteristic example, the mobile irradiation control system 110 mcan include a mobile phone 111 m that can be attached to the rest of theophthalmic stimulator 100 m that is installed in a medical office as adesktop office device. As such, the irradiation source 120 m and theirradiation delivery system 130 m can themselves be a movable, lightbench-top device that is mobile, but less mobile than the fully mobileplatform 111 m, or mobile phone 111 m. Accordingly, in some embodimentsthey can be referred to as the mobile irradiation source 120 m, and themobile irradiation delivery system 130 m.

The mobile camera 114 m of the mobile phone 111 m can image the iris 11and pupil 13 of a patient who is looking into the camera 114 m. Themobile irradiation controller 110 cm, implemented on the mobile phone111 m, can display the image of the pupil on the screen of the mobilephone 111 m, and also electronically overlay a proposed irradiationpattern 210. The irradiation control application can then invite thedoctor, or user, to modify the pattern within some limits of safety asthe image-based input, such as to move the inner and the outer radiiRp(inner) and Rp(outer), while making sure that the pattern 210 remainson the iris 11. Once the modification input is received, possiblytogether with some treatment parameters, the irradiation controlapplication on the mobile phone 111 m can send an irradiation controlsignal to the irradiation source 120 m and the irradiation deliverysystem 130 m wirelessly with a Bluetooth channel. In response, theirradiation source 120 m and the irradiation delivery system 130 m cangenerate and deliver the patterned irradiation 200 p onto the imagediris 11.

FIG. 13A illustrates that in some embodiments, the mobile irradiationcontrol system 110 m can include an image processor 114 ipm, to receivethe image of the iris from the imaging system 114 m, and to generate theimage-based input based on a processing of the image of the iris. Insome designs, this image processor 114 ipm can determine the inner andouter radii Rp(inner) and Rp(outer) of the ring pattern 210, as well asthe treatment parameters. There can be hybrid systems, where the imageprocessor 114 ipm performs the above determinations, however, a userinterface 118 of the mobile telephone 111 m still prompts a surgeon oroperator to approve the displayed choices of the imager processor 114ipm, as a safety measure.

In some implementations, the image processor 114 ipm can generate theimage-based input by correlating an alignment pattern 138 with thegenerated image of the iris, in analogy to the alignment system 135 inFIG. 12C. Subsequently, the mobile irradiation control system 110 m canbe configured to generate the irradiation control signal according tothe received image-based input that includes a misalignment-warningsignal, an alignment-guidance signal, or an irradiation-stop signal, ifa misalignment is detected. In a characteristic case, the mobile phone111 m can alert the ophthalmologist that a misalignment was detected,possibly also generating an alignment-guidance signal, such as which wayto move the eye 1, or the irradiation delivery system 130 to realign theeye and the irradiation delivery system 130.

The ability of the mobile platform 111 m to communicate can play a veryuseful role in some implementations. In these designs, the mobileirradiation control system 110 m can include an on-board communicationapplication, to receive the image of the iris from the imaging system114 m, to communicate the received image to a central station 410 havingan image processor, and to receive the image-based input from imageprocessor of the central station 410.

FIGS. 13B-C illustrate advanced embodiments, where not the mobile phone111 m is attached to the rest of the ophthalmic stimulator 100 m, butthe rest of the ophthalmic stimulator 100 m is attached to the mobilephone 111 m, to create a fully mobile ophthalmic stimulator 100 m.

FIG. 13B illustrates a design of the mobile ophthalmic stimulator 100 m,wherein the irradiation source 120 m and the irradiation delivery system130 m are part of a small, compact irradiation device 120 m/130 m; andthe mobile irradiation control system 110 m is coupled to theirradiation device 120 m/130 m to send the irradiation control signal byat least one of an electronic coupling, an electric coupling, a wirelesscoupling, and an optical coupling.

In the shown example, the irradiation source 120 m and the irradiationdelivery system 130 m are configured to be electrically coupled to, andmechanically attached to the mobile irradiation control system 110 m.For example, the irradiation device 120 m/130 m can be plugged into oneof the ports of the mobile phone 111 m, such as into the USB port, orinto the headphone jack, or the power charging port. In another example,the irradiation device 120 m/130 m can be attached to the mobile phone111 m by a clip, mini-pliers, or pincer.

FIG. 13C illustrates an example, in which the irradiation source 120 mis a light source of the mobile irradiation control system 110 m, andthe irradiation delivery system 130 m is mechanically attached to themobile irradiation control system 110 m, to receive a light, generatedby the irradiation source 120 m. In a characteristic example, theflashlight of the mobile phone 111 m itself can be used as theirradiation source 120 m. The flashlight of the mobile phone 111 m, ofcourse, needs to be calibrated to gain control over the power irradiatedby its irradiation 200, and possibly filtered or dampened. Nevertheless,using the imaging capabilities of the mobile phones 111 m and theirflashlight can make the mobile ophthalmic stimulator 100 m much cheaperand compact, and therefore suitable for being carried by a patient as apersonal accessory. This aspect can be very useful if irradiationtreatments are utilized that cause a temporary constriction of the pupilthat lasts less than a day, and thus a once-a-day application in themorning does not secure the pupil constriction for the entire day. Suchtreatments may need to be refreshed as the day goes on. A portable,personalized, mobile phone-based ophthalmic stimulator 100 m can be theanswer for the need for refreshing treatments during the day.

Obviously, safety is a high priority consideration for the mobileembodiments of the stimulator 100 m that are not operated by trainedophthalmologists. Moreover, achieving and preserving alignment for theduration of the treatment also becomes an elevated challenge for mobilestimulator 100 m. Mobile stimulators 100 m can address these concerns,by practicing the method, or process 540, illustrated in FIG. 16D. It isrecalled here, that in step 543, if the imaging system 114, thealignment system 116 c, or the eye tracker 116 d sense a misalignment,then they can induce the generation of a feedback-based irradiationcontrol signal that makes the irradiation source 120 m stop theirradiation 200. Implementing this imaging-triggered “safety stop”process makes mobile stimulators 100 m safe, and minimizes undesirableretinal exposure.

Moreover, if the eye gets realigned, for example, because the user moveseither the hand-held mobile phone 111 m, or moves her/his gaze, then theimaging system 114, or its equivalents, can sense the realignment instep 545, and the irradiation controller 110 m can cause the restart theirradiation. These stop 543—restart 545 steps can be performedrepeatedly, as, for example, the handheld mobile phone 111 m is movingin the patient's hand.

An interrupted, or multiply interrupted irradiation treatment may takelonger to achieve the temperature rise required for the desired pupilconstriction, and to administer the treatment for the time necessary forefficacy. Therefore, mobile stimulators 100 m can include at least oneof a thermal camera, an infrared camera and a thermal sensor 116 b, totrack an amount of time a treatment region of the iris had a temperaturein a predetermined range. In an example, the irradiation controller 110m may add up the multiply interrupted time-segments, when the treatmentregion of the iris was at the prescribed temperature, and ensure thatthe treatment region has been held at the prescribed temperature rangefor the time interval necessary to achieve the targeted pupilconstriction. For example, the IR sensor 116 b can track that thetreated ring 210 r of the iris 11 remains at 55 Celsius for a prescribedtime, such as for 20 seconds, or for 40 seconds, in order to achieve apupil constriction that will last all day.

In some embodiments, the safety stop 543—restart 545 steps can be alsoperformed under the control of the central station 410. In suchembodiments, it can be the image processor of the central station 410that senses the misalignment of the patterned irradiation relative tothe iris or the pupil, as well as that senses the realignment, promptingthe generation of the restart command.

Finally, the central station 410 can perform monitoring functions over aseries of treatments performed by the mobile ophthalmic stimulator 100m. In some embodiments, the mobile stimulator 100 m can be configured totake and send the image of the iris to the central station 410 formonitoring, to receive a monitoring-based control signal from thecentral station, and to generate the irradiation control signal inaccordance with the received monitoring-based control signal. Forexample, the images, sent by the stimulator 100 m, can be analyzed bythe central station 410. This analysis can recognize that the treatmentis inducing an undesirable effect in the retina over the term of severaltreatments. In such case, the central station may send out amonitoring-based control signal to the mobile stimulator 100 m to eitherprevent the user from administering further treatments, or to change atreatment parameter, such as to reduce a power or intensity of thepatterned irradiation 200 p. Such central station-related systems aredescribed next.

FIG. 14 illustrates a networked system 400 of ophthalmic stimulators fortemporarily constricting eye-pupils. The networked system 400, or mobilenetwork 400, can include a set of mobile ophthalmic stimulators 100 m-1,100 m-2, . . . 100 m-N, collectively referred to as mobile ophthalmicstimulators 100 m-i, each mobile ophthalmic stimulator 100 m-i includinga mobile irradiation control system 110 m-i, to generate an irradiationcontrol signal; an irradiation source 120 m-i, coupled to theirradiation control system 110 m-i, to generate an irradiation; and anirradiation delivery system 130 m-i, coupled to the mobile irradiationcontrol system 110 m-i, to receive the irradiation from the irradiationsource 120 m-i, and to deliver a patterned irradiation 200 p to an irisof the eye; wherein the mobile irradiation control system 110 m-icontrols at least one of the irradiation source 120 m-i and theirradiation delivery system 130 m-i with the irradiation control signalso that the patterned irradiation 200 p causes a temporary constrictionof the pupil of the eye, without causing a permanent constriction of thepupil.

The networked system 400 further includes a central station 410,including a central image processor, wherein the mobile irradiationcontrol systems 110 m-i of the mobile ophthalmic stimulators 100 m-i andthe central station 410 are configured to communicate through acommunication network. In this section, the term mobile ophthalmicstimulator 100 m-i encompasses all embodiments described in relation toFIGS. 13A-C.

In embodiments of the networked system 400, each mobile irradiationcontrol system 110 m-i can include a mobile communication platform 111m-i, including at least one of a mobile telephone, a mobilecommunication device, and a mobile tablet; and a mobile irradiationcontroller 110 cm-i, implemented on the mobile communication platform111 m-i, to generate the irradiation control signal. In embodiments, themobile communication platforms 111 m-i can include a memory, to store asoftware implementation of the mobile irradiation controller 110 cm-i; aprocessor, to execute the stored software implementation of the mobileirradiation controller 110 cm-i; and a user interface, to receive inputfrom a user in relation to an operation of the memory and the processor.In embodiments, the mobile ophthalmic stimulators can be configured toincrease a temperature of a treatment region of the iris to a range of45-60 degrees Celsius.

Each mobile irradiation control system 110 m-i can include an imagingsystem 114 m-i, to generate the irradiation control signal by generatingan image of the iris of the eye by the imaging system 114 m-i, receivingan image-based input, and generating the irradiation control signal tocontrol at least one of the irradiation 120 m-i source and theirradiation delivery system 130 m-i to deliver the patterned irradiation200 p according to the received image-based input.

In some characteristic embodiments, the mobile irradiation controlsystems 11 m-i can include an image processor 114 ipm-i, to receive theimage of the iris from the imaging system, and to generate theimage-based input based on a processing of the image of the iris. InFIG. 14, the image processors 114 ipm-i are not shown for scarcity ofspace. Embodiments of the image processors 114 ipm-i have been shown anddescribed earlier, such as in FIG. 6A. As described earlier, theon-board image processors 114 ipm-i, can generate an image-based inputfor the irradiation control systems 110 m-i, which then can control therest of the mobile ophthalmic stimulators 100 m-i accordingly. In suchembodiments, the communications of the mobile ophthalmic stimulators 100m-i with the central station 410 can be a recording of the results ofthe image processing, and the record of the treatments performed by themobile ophthalmic stimulators 100 m-i.

In other embodiments, each ophthalmic stimulator 100 m-i can beconfigured to send the image of the iris to the central station 410; andthe central station 410 can be configured to analyze the received imageby a central image processor 410 ip, and to respond to the sendingmobile ophthalmic stimulator 100 m-i with the image-based input based onthe analysis. This communication and analysis can be real-time,actionable. In other cases, it can be a post-treatment, recording theactions type communication.

In real-time embodiments, each ophthalmic stimulator 100 m-i can beconfigured to generate and to send the image of the iris to the centralstation 410 before the irradiation delivery system delivers 130 m-i thepatterned irradiation to the iris; and the central station 410 can beconfigured to respond to the sending ophthalmic stimulator 100 m-i withthe image-based input that indicates whether the central station 410authorizes the irradiation delivery system 130-i of the ophthalmicstimulator 100 m-i to deliver the patterned irradiation to the iris.

Clearly, such preauthorization-based networked systems 400 have safetybenefits, as when the patient intends to use the mobile ophthalmicstimulator 100 m-i, the stimulator 100 m-i first needs to send an imageof the iris to be treated to the central station 410. This gives achance for the central image processor 410 ip to analyze the image ofthe iris, and if it finds anything that raises a medical concern, suchas a shape change, or an unexpected discoloration, the central station410 can communicate a “Treatment not authorized” imaging-based input tothe mobile stimulator 100 m-i, which then prevents the mobile stimulator100 m-i from irradiating the iris when medical concerns have been raisedby the image analysis.

In a related embodiment of the networked system 400, each ophthalmicstimulator 100 m-i can be configured to generate, and to send, the imageof the iris to the central station 410 before the irradiation deliverysystem 130 m-i delivers the patterned irradiation 200 p to the iris; andthe central station 410 can be configured to respond to the sendingmobile ophthalmic stimulator 100 m-i with the image-based input thatindicates irradiation parameters to be used by the irradiation deliverysystem 130 m-i of the mobile ophthalmic stimulator 100 m-i whendelivering the patterned irradiation to the iris.

The safety aspects of this embodiment are quite similar to the previousone. One of the differences is that the imaging-based input from thecentral station is not a binary “authorized-not authorized” input, but aquantitative input, nuanced input. In a characteristic example, thecentral image processor 410 ip can notice a small discoloration of theiris in the image, sent in by the mobile stimulator 100 m-i. However,the discoloration may be small enough so that a hard-stop “Treatment notauthorized” input may be excessive. In such cases, the central imageprocessor 410 ip can respond instead by a message of “Reduce power ofirradiation in next treatment” input. In some embodiments, the centralimage processor 410 ip can even schedule a follow-up imaging, to checkhow the iris reacted to the reduced power irradiation: was the reductionsufficient to eliminate the discoloration, or further analysis isneeded.

In some embodiments, the central imaging processor 410 ip of the centralstation 410 can be configured to perform a medical analysis of the imageof the iris, and to respond to the sending ophthalmic stimulator 100 m-iwith the image-based input that indicates if a negative medicalcondition was found by the analysis. The medical analysis can take placein a number of ways. The central station 410 can engage in an automatedmedical analysis, where for example past images of the iris, recalledfrom a memory, are compared to the present image. Or, the image of theiris can be compared to a database, compiled from tracking a largenumber of irises. Some embodiments can use artificial intelligencesystems to recognize, and to evaluate the negative medical condition,such as an inflammation of the iris. Or, the image processor can flagthe image, and request an opinion or analysis by a human specialist.

The negative medical condition can also be a wide range of conditions,including a change of color of the iris, a change of an opticalcharacteristic, and a change of shape of the iris.

In some advanced embodiments, the mobile ophthalmic stimulators 100 m-ican be configured to test the iris 11 and to send a test result to thecentral station 410; and the central station 410 can be configured toperform a medical analysis of the test result, and to respond to thesending mobile ophthalmic stimulators 100 m-i with the image-based inputthat indicates if a negative medical condition was found by theanalysis. The mentioned test of the iris can include irradiating theiris with a test irradiation, and measuring a constriction of the pupilin response to the test irradiation. The performing a medical analysiscan include recalling a previous test result, as mentioned. Finally, thedetection of a negative medical condition can include comparing the testresult with the previous test result, and finding the test result lessacceptable than the previous test result. In other embodiments, thecomparison can be made not with past measurements or tests on the sameiris, but to a database of a large number of irises. This database canbe organized into groups according to many shared traits, so thatpatients with comparable medical situations and characteristics arecompared by the database.

As mentioned in relation to the mobile stimulators 100 m of FIGS. 13A-Cearlier, in another class of embodiments, the mobile ophthalmicstimulators 100 m-i can be configured to send alignment data to thecentral station 410 regarding an alignment of the patterned irradiation200 p with at least one of the iris and the pupil; and the centralstation 410 can be configured to evaluate the alignment data; and tosend a control signal to stop the patterned irradiation 200 p when thepatterned irradiation 200 p is evaluated to be misaligned with at leastone of the iris and the pupil. In some embodiments, the alignment datacan be generated by the imaging system 114 m. In others, by variousembodiments of the alignment system 135, possibly using the patientinterface 137 and the alignment pattern 138. In imaging-basedembodiments, the control signal can be analogous to the image-basedinput, described earlier.

Generally speaking, in some embodiments of the networked system 400 themobile irradiation control systems 110 m-i of the mobile ophthalmicstimulators 100 m-i and the central station 410 can be configured tocommunicate regarding safety monitoring of the irradiations andtreatments by an interface, or dedicated block or code 413. This is ageneric concept that encompasses communication regarding all majorsafety monitoring channels, including expected and unexpected medicaloutcomes, treatment parameters, proper alignment, and test results, fromthe viewpoint of safety. As described, the safety monitoring can resultprompting a dedicated block, processor, or code 416 to signal or orderpreventive shutdowns of the mobile stimulators.

Analogous communications can be performed by a treatment outcomemonitoring block, dedicated processor, or code 412. Communications abouttreatment outcomes can then be used by a block, dedicated processor, orpiece of code 415, to develop and assemble a statistics of the treatmentoutcomes with the purpose of improving the understanding and theoperations of the networked system 400 for the benefit of the patients.This communication channel can, of course, also be useful for pushingout new versions of treatment software from the central station 410 tothe individual mobile stimulators 100 m-i.

These communications may not be real time, or actionable. In someembodiments, for example, the mobile irradiation control systems 110 m-iof the mobile ophthalmic stimulators 100 m-i and the central station 410can be configured to communicate treatment outcomes after an irradiationhas been performed. In other embodiments, they can be configured tocommunicate regarding patient data, which then can be stored in adedicated processor and memory 411.

While this document contains many specifics, these should not beconstrued as limitations on the scope of an invention or of what may beclaimed, but rather as descriptions of features specific to particularembodiments of the invention. Certain features that are described inthis document in the context of separate embodiments can also beimplemented in combination in a single embodiment. Conversely, variousfeatures that are described in the context of a single embodiment canalso be implemented in multiple embodiments separately or in anysuitable subcombination. Moreover, although features may be describedabove as acting in certain combinations and even initially claimed assuch, one or more features from a claimed combination can in some casesbe excised from the combination, and the claimed combination may bedirected to a subcombination or a variation of a subcombination.

The invention claimed is:
 1. A networked system of mobile ophthalmicstimulators for temporarily constricting eye-pupils, comprising: a setof mobile ophthalmic stimulators, each mobile ophthalmic stimulatorincluding a mobile irradiation control system, to generate anirradiation control signal; an irradiation source, coupled to theirradiation control system, to generate an irradiation; and anirradiation delivery system, coupled to the mobile irradiation controlsystem, to receive the irradiation from the irradiation source, andadapted to deliver a patterned irradiation with a power density in arange of 0.1-1000 mW/cm·sup.2 to an iris of an eye; wherein the mobileirradiation control system controls at least one of the irradiationsource and the irradiation delivery system with the irradiation controlsignal so that the patterned irradiation with the power density causes atemporary constriction of the pupil of the eye including an at least 5%reduction of a radius of the pupil that lasts between one hour and oneday in response to delivering the patterned irradiation for a timeperiod in a range of 1-100 seconds to minimize retinal exposure; and acentral station, wherein the mobile irradiation control systems of theof the ophthalmic stimulators and the central station are configured tocommunicate through a communication network.
 2. The networked system ofclaim 1, each mobile irradiation control system comprising: a mobilecommunication platform, including at least one of a mobile telephone, amobile communication device, and a mobile tablet; and a mobileirradiation controller, installed on the mobile communication platform,to generate the irradiation control signal.
 3. The networked system ofclaim 2, the mobile communication platforms comprising: a memory, tostore a software implementation of the mobile irradiation controller; aprocessor, to execute the software implementation of the mobileirradiation controller; and a user interface, to receive input from auser in relation to an operation of the memory and the processor.
 4. Thenetworked system of claim 1, wherein: the mobile ophthalmic stimulatoris configured to increase a temperature of a treatment region of theiris to a range of 45-60 degrees Celsius.
 5. The networked system ofclaim 1, the mobile irradiation control systems comprising: an imagingsystem, to generate the irradiation control signal by generating animage of the iris of the eye by the imaging system, receiving animage-based input, and generating the irradiation control signal tocontrol at least one of the irradiation source and the irradiationdelivery system to deliver the patterned irradiation according to thereceived image-based input.
 6. The networked system of claim 5, themobile irradiation control systems comprising: an image processor, toreceive the image of the iris from the imaging system, and to generatethe image-based input based on a processing of the image of the iris. 7.The networked system of claim 5, wherein: each mobile ophthalmicstimulator is configured to send the image of the iris to the centralstation; and the central station is configured to analyze the receivedimage by a central image processor, and to respond to the sendingophthalmic stimulator with the image-based input based on the analysis.8. The networked system of claim 7, wherein: each mobile ophthalmicstimulator is configured to generate and to send the image of the iristo the central station before the irradiation delivery system deliversthe patterned irradiation to the iris; and the central station isconfigured to respond to the sending mobile ophthalmic stimulator withthe image-based input that indicates authorization of the irradiationdelivery system of the ophthalmic stimulator by the central station todeliver the patterned irradiation to the iris.
 9. The networked systemof claim 7, wherein: each mobile ophthalmic stimulator is configured togenerate and to send the image of the iris to the central station beforethe irradiation delivery system delivers the patterned irradiation tothe iris; and the central station is configured to respond to thesending mobile ophthalmic stimulator with the image-based input thatindicates irradiation parameters to be used by the irradiation deliverysystem of the ophthalmic stimulator when delivering the patternedirradiation to the iris.
 10. The networked system of claim 7, wherein:the central imaging processor of the central station is configured toperform a medical analysis of the image of the iris, and to respond tothe sending mobile ophthalmic stimulator with the image-based input thatindicates a finding of a negative medical condition by the analysis. 11.The networked system of claim 10, wherein: the medical analysis includesrecalling a previous image of the imaged iris from a memory and thenegative medical condition is one of a change of color of the iris, achange of an optical characteristic, and a change of shape of the iris.12. The networked system of claim 5, wherein: the mobile ophthalmicstimulators are configured to test the iris and to send a test result tothe central station; and the central station is configured to perform amedical analysis of the test result, and to respond to the sendingmobile ophthalmic stimulators with the image-based input that indicatesa finding of a negative medical condition by the analysis.
 13. Thenetworked system of claim 12, wherein: the test of the iris includesirradiating the iris with a test irradiation, and measuring aconstriction of the pupil in response to the test irradiation; theperforming the medical analysis includes recalling a previous testresult; and the finding of the negative medical condition includescomparing the test result with the previous test result, and finding thetest result less acceptable than the previous test result.
 14. Thenetworked system of claim 1, wherein: the mobile ophthalmic stimulatorsare configured to send alignment data to the central station regardingthe alignment of the patterned irradiation with at least one of the irisand the pupil; and the central station is configured to evaluate thealignment data; and to send a control signal to stop the patternedirradiation when the patterned irradiation is evaluated to be misalignedwith at least one of the iris and the pupil.
 15. The networked system ofclaim 1, wherein: the mobile irradiation control systems of the mobileophthalmic stimulators and the central station are configured tocommunicate treatment outcomes.
 16. The networked system of claim 1,wherein: the mobile irradiation control systems of the mobile ophthalmicstimulators and the central station are configured to communicateregarding safety monitoring of treatments.
 17. The networked system ofclaim 1, wherein: the mobile irradiation control systems of the mobileophthalmic stimulators and the central station are configured tocommunicate regarding patient data.